DNA Methylation in Promoter Region as Biomarkers in Prostate Cancer

Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 863)

Abstract

The prostate gland is the most common site of cancer and the second leading cause of cancer death in American men. Recent emerging molecular biological technologies help us to know that epigenetic alterations such as DNA methylation within the regulatory (promoter) regions of genes are associated with transcriptional silencing in cancer. Promoter hypermethylation of critical pathway genes could be potential biomarkers and therapeutic targets for prostate cancer. In this chapter, we updated current information on methylated genes associated with the development and progression of prostate cancer. Over 40 genes have been investigated for methylation in promoter region in prostate cancer. These methylated genes are involved in critical pathways, such as DNA repair, metabolism, and invasion/metastasis. The role of hypermethylated genes in regulation of critical pathways in prostate cancer is discussed. These findings may provide new information of the pathogenesis, the exciting potential to be predictive and to provide personalized treatment of prostate cancer. Indeed, some epigenetic alterations in prostate tumors are being translated into clinical practice for therapeutic use.

Key words

Prostate cancer DNA methylation Epigenetic variation Biomarker 

References

  1. 1.
    Crawford, E. D. (2003) Epidemiology of prostate cancer, Urology 62, 3–12.PubMedCrossRefGoogle Scholar
  2. 2.
    Jemal, A., Siegel, R., Xu, J., and Ward, E. (2010) Cancer statistics, 2010, CA Cancer J Clin 60, 277–300.PubMedCrossRefGoogle Scholar
  3. 3.
  4. 4.
    Baylin, S. B., and Herman, J. G. (2000) DNA hypermethylation in tumorigenesis: epigenetics joins genetics, Trends Genet 16, 168–174.PubMedCrossRefGoogle Scholar
  5. 5.
    Smiraglia, D. J., and Plass, C. (2002) The study of aberrant methylation in cancer via restriction landmark genomic scanning, Oncogene 21, 5414–5426.PubMedCrossRefGoogle Scholar
  6. 6.
    Rush, L. J., Dai, Z., Smiraglia, D. J., Gao, X., Wright, F. A., Fruhwald, M., Costello, J. F., Held, W. A., Yu, L., Krahe, R., Kolitz, J. E., Bloomfield, C. D., Caligiuri, M. A., and Plass, C. (2001) Novel methylation targets in de novo acute myeloid leukemia with prevalence of chromosome 11 loci, Blood 97, 3226–3233.PubMedCrossRefGoogle Scholar
  7. 7.
    Costello, J. F., Fruhwald, M. C., Smiraglia, D. J., Rush, L. J., Robertson, G. P., Gao, X., Wright, F. A., Feramisco, J. D., Peltomaki, P., Lang, J. C., Schuller, D. E., Yu, L., Bloomfield, C. D., Caligiuri, M. A., Yates, A., Nishikawa, R., Su Huang, H., Petrelli, N. J., Zhang, X., O’Dorisio, M. S., Held, W. A., Cavenee, W. K., and Plass, C. (2000) Aberrant CpG-island methylation has non-random and tumour-type-specific patterns, Nat Genet 24, 132–138.PubMedCrossRefGoogle Scholar
  8. 8.
    Baylin, S. B., Herman, J. G., Graff, J. R., Vertino, P. M., and Issa, J. P. (1998) Alterations in DNA methylation: a fundamental aspect of neoplasia, Adv Cancer Res 72, 141–196.PubMedCrossRefGoogle Scholar
  9. 9.
    Di Croce, L., Raker, V. A., Corsaro, M., Fazi, F., Fanelli, M., Faretta, M., Fuks, F., Lo Coco, F., Kouzarides, T., Nervi, C., Minucci, S., and Pelicci, P. G. (2002) Methyltransferase recruitment and DNA hypermethylation of target promoters by an oncogenic transcription factor, Science 295, 1079–1082.PubMedCrossRefGoogle Scholar
  10. 10.
    Yan, P. S., Shi, H., Rahmatpanah, F., Hsiau, T. H., Hsiau, A. H., Leu, Y. W., Liu, J. C., and Huang, T. H. (2003) Differential distribution of DNA methylation within the RASSF1A CpG island in breast cancer, Cancer Res 63, 6178–6186.PubMedGoogle Scholar
  11. 11.
    Graff, J. R., Herman, J. G., Myohanen, S., Baylin, S. B., and Vertino, P. M. (1997) Mapping patterns of CpG island methylation in normal and neoplastic cells implicates both upstream and downstream regions in de novo methylation, J Biol Chem 272, 22322–22329.PubMedCrossRefGoogle Scholar
  12. 12.
    Esteller, M. (2000) Epigenetic lesions causing genetic lesions in human cancer: promoter hypermethylation of DNA repair genes, Eur J Cancer 36, 2294–2300.PubMedCrossRefGoogle Scholar
  13. 13.
    Bachman, K. E., Herman, J. G., Corn, P. G., Merlo, A., Costello, J. F., Cavenee, W. K., Baylin, S. B., and Graff, J. R. (1999) Methylation-associated silencing of the tissue inhibitor of metalloproteinase-3 gene suggest a suppressor role in kidney, brain, and other human cancers, Cancer Res 59, 798–802.PubMedGoogle Scholar
  14. 14.
    Toyota, M., Ohe-Toyota, M., Ahuja, N., and Issa, J.-P. J. (2000) Distinct genetic profiles in colorectal tumors with or without the CpG island methylator phenotype, PNAS 97, 710–715.PubMedCrossRefGoogle Scholar
  15. 15.
    Stirzaker, C., Millar, D. S., Paul, C. L., Warnecke, P. M., Harrison, J., Vincent, P. C., Frommer, M., and Clark, S. J. (1997) Extensive DNA methylation spanning the Rb promoter in retinoblastoma tumors, Cancer Res 57, 2229–2237.PubMedGoogle Scholar
  16. 16.
    Deng, G., Chen, A., Hong, J., Chae, H. S., and Kim, Y. S. (1999) Methylation of CpG in a small region of the hMLH1 promoter invariably correlates with the absence of gene expression, Cancer Res 59, 2029–2033.PubMedGoogle Scholar
  17. 17.
    Gonzalgo, M. L., Bender, C. M., You, E. H., Glendening, J. M., Flores, J. F., Walker, G. J., Hayward, N. K., Jones, P. A., and Fountain, J. W. (1997) Low frequency of p16/CDKN2A methylation in sporadic melanoma: comparative approaches for methylation analysis of primary tumors, Cancer Res 57, 5336–5347.PubMedGoogle Scholar
  18. 18.
    Gonzalez-Zulueta, M., Bender, C. M., Yang, A. S., Nguyen, T., Beart, R. W., Van Tornout, J. M., and Jones, P. A. (1995) Methylation of the 5′ CpG island of the p16/CDKN2 tumor suppressor gene in normal and transformed human tissues correlates with gene silencing, Cancer Res 55, 4531–4535.PubMedGoogle Scholar
  19. 19.
    Patra, S. K., and Bettuzzi, S. (2007) Epigenetic DNA-methylation regulation of genes coding for lipid raft-associated components: a role for raft proteins in cell transformation and cancer progression (review), Oncol Rep 17, 1279–1290.PubMedGoogle Scholar
  20. 20.
    Cui, J., Rohr, L. R., Swanson, G., Speights, V. O., Maxwell, T., and Brothman, A. R. (2001) Hypermethylation of the caveolin-1 gene promoter in prostate cancer, Prostate 46, 249–256.PubMedCrossRefGoogle Scholar
  21. 21.
    Bachmann, N., Haeusler, J., Luedeke, M., Kuefer, R., Perner, S., Assum, G., Paiss, T., Hoegel, J., Vogel, W., and Maier, C. (2008) Expression changes of CAV1 and EZH2, located on 7q31 approximately q36, are rarely related to genomic alterations in primary prostate carcinoma, Cancer Genet Cytogenet 182, 103–110.PubMedCrossRefGoogle Scholar
  22. 22.
    Woodson, K., Hanson, J., and Tangrea, J. (2004) A survey of gene-specific methylation in human prostate cancer among black and white men, Cancer Lett 205, 181–188.PubMedCrossRefGoogle Scholar
  23. 23.
    Karam, J. A., Lotan, Y., Roehrborn, C. G., Ashfaq, R., Karakiewicz, P. I., and Shariat, S. F. (2007) Caveolin-1 overexpression is associated with aggressive prostate cancer recurrence, Prostate 67 614–622.PubMedCrossRefGoogle Scholar
  24. 24.
    Di Vizio, D., Sotgia, F., Williams, T. M., Hassan, G. S., Capozza, F., Frank, P. G., Pestell, R. G., Loda, M., Freeman, M. R., and Lisanti, M. P. (2007) Caveolin-1 is required for the upregulation of fatty acid synthase (FASN), a tumor promoter, during prostate cancer progression, Cancer Biol Ther 6, 1263–1268.PubMedGoogle Scholar
  25. 25.
    Jeronimo, C., Henrique, R., Hoque, M. O., Mambo, E., Ribeiro, F. R., Varzim, G., Oliveira, J., Teixeira, M. R., Lopes, C., and Sidransky, D. (2004) A quantitative promoter methylation profile of prostate cancer, Clin Cancer Res 10, 8472–8478.PubMedCrossRefGoogle Scholar
  26. 26.
    Konishi, N., Nakamura, M., Kishi, M., Nishimine, M., Ishida, E., and Shimada, K. (2002) Heterogeneous methylation and deletion patterns of the INK4a/ARF locus within prostate carcinomas, Am J Pathol 160, 1207–1214.PubMedCrossRefGoogle Scholar
  27. 27.
    Nguyen, T. T., Nguyen, C. T., Gonzales, F. A., Nichols, P. W., Yu, M. C., and Jones, P. A. (2000) Analysis of cyclin-dependent kinase inhibitor expression and methylation patterns in human prostate cancers, Prostate 43, 233–242.PubMedCrossRefGoogle Scholar
  28. 28.
    Schwarzenbach, H., Chun, F. K., Isbarn, H., Huland, H., and Pantel, K. (2010) Genomic profiling of cell-free DNA in blood and bone marrow of prostate cancer patients, J Cancer Res Clin Oncol.Google Scholar
  29. 29.
    Maruyama, R., Toyooka, S., Toyooka, K. O., Virmani, A. K., Zochbauer-Muller, S., Farinas, A. J., Minna, J. D., McConnell, J., Frenkel, E. P., and Gazdar, A. F. (2002) Aberrant promoter methylation profile of prostate cancers and its relationship to clinicopathological features, Clin Cancer Res 8, 514–519.PubMedGoogle Scholar
  30. 30.
    Yegnasubramanian, S., Kowalski, J., Gonzalgo, M. L., Zahurak, M., Piantadosi, S., Walsh, P. C., Bova, G. S., De Marzo, A. M., Isaacs, W. B., and Nelson, W. G. (2004) Hypermethylation of CpG islands in primary and metastatic human prostate cancer, Cancer Res 64 1975–1986.PubMedCrossRefGoogle Scholar
  31. 31.
    Hoque, M. O., Topaloglu, O., Begum, S., Henrique, R., Rosenbaum, E., Van Criekinge, W., Westra, W. H., and Sidransky, D. (2005) Quantitative methylation-specific polymerase chain reaction gene patterns in urine sediment distinguish prostate cancer patients from control subjects, J Clin Oncol 23, 6569–6575.PubMedCrossRefGoogle Scholar
  32. 32.
    Gu, K., Mes-Masson, A. M., Gauthier, J., and Saad, F. (1998) Analysis of the p16 tumor suppressor gene in early-stage prostate cancer, Mol Carcinog 21, 164–170.PubMedCrossRefGoogle Scholar
  33. 33.
    Herman, J. G., Merlo, A., Mao, L., Lapidus, R. G., Issa, J. P., Davidson, N. E., Sidransky, D., and Baylin, S. B. (1995) Inactivation of the CDKN2/p16/MTS1 gene is frequently associated with aberrant DNA methylation in all common human cancers, Cancer Res 55, 4525–4530.PubMedGoogle Scholar
  34. 34.
    Jarrard, D. F., Bova, G. S., Ewing, C. M., Pin, S. S., Nguyen, S. H., Baylin, S. B., Cairns, P., Sidransky, D., Herman, J. G., and Isaacs, W. B. (1997) Deletional, mutational, and methylation analyses of CDKN2 (p16/MTS1) in primary and metastatic prostate cancer, Genes Chromosomes Cancer 19, 90-96.PubMedCrossRefGoogle Scholar
  35. 35.
    Florl, A. R., Steinhoff, C., Muller, M., Seifert, H. H., Hader, C., Engers, R., Ackermann, R., and Schulz, W. A. (2004) Coordinate hypermethylation at specific genes in prostate carcinoma precedes LINE-1 hypomethylation, Br J Cancer 91, 985–994.PubMedGoogle Scholar
  36. 36.
    Roupret, M., Hupertan, V., Yates, D. R., Catto, J. W., Rehman, I., Meuth, M., Ricci, S., Lacave, R., Cancel-Tassin, G., de la Taille, A., Rozet, F., Cathelineau, X., Vallancien, G., Hamdy, F. C., and Cussenot, O. (2007) Molecular detection of localized prostate cancer using quantitative methylation-specific PCR on urinary cells obtained following prostate massage, Clin Cancer Res 13, 1720–1725.PubMedCrossRefGoogle Scholar
  37. 37.
    Higuchi, T., Nakamura, M., Shimada, K., Ishida, E., Hirao, K., and Konishi, N. (2008) HRK inactivation associated with promoter methylation and LOH in prostate cancer, Prostate 68, 105–113.PubMedCrossRefGoogle Scholar
  38. 38.
    Nakamura, M., Watanabe, T., Klangby, U., Asker, C., Wiman, K., Yonekawa, Y., Kleihues, P., and Ohgaki, H. (2001) p14ARF deletion and methylation in genetic pathways to glioblastomas, Brain Pathol 11, 159–168.PubMedCrossRefGoogle Scholar
  39. 39.
    Lin, H. H., Ke, H. L., Huang, S. P., Wu, W. J., Chen, Y. K., and Chang, L. L. (2009) Increase sensitivity in detecting superficial, low grade bladder cancer by combination analysis of hypermethylation of E-cadherin, p16, p14, RASSF1A genes in urine, Urol Oncol.Google Scholar
  40. 40.
    Chim, C. S., Chan, W. W., and Kwong, Y. L. (2008) Epigenetic dysregulation of the DAP kinase/p14/HDM2/p53/Apaf-1 apoptosis pathway in acute leukaemias, J Clin Pathol 61, 844–847.PubMedCrossRefGoogle Scholar
  41. 41.
    Calmon, M. F., Colombo, J., Carvalho, F., Souza, F. P., Filho, J. F., Fukuyama, E. E., Camargo, A. A., Caballero, O. L., Tajara, E. H., Cordeiro, J. A., and Rahal, P. (2007) Methylation profile of genes CDKN2A (p14 and p16), DAPK1, CDH1 and ADAM23 in head and neck cancer, Cancer Genet Cytogenet 173, 31–37.PubMedCrossRefGoogle Scholar
  42. 42.
    Konishi, N., Nakamura, M., Kishi, M., Nishimine, M., Ishida, E., and Shimada, K. (2002) DNA hypermethylation status of multiple genes in prostate adenocarcinomas, Jpn J Cancer Res 93, 767–773.PubMedCrossRefGoogle Scholar
  43. 43.
    Yam, C. H., Fung, T. K., and Poon, R. Y. (2002) Cyclin A in cell cycle control and cancer, Cell Mol Life Sci 59, 1317–1326.PubMedCrossRefGoogle Scholar
  44. 44.
    Yang, N., Eijsink, J. J., Lendvai, A., Volders, H. H., Klip, H., Buikema, H. J., van Hemel, B. M., Schuuring, E., van der Zee, A. G., and Wisman, G. B. (2009) Methylation markers for CCNA1 and C13ORF18 are strongly associated with high-grade cervical intraepithelial neoplasia and cervical cancer in cervical scrapings, Cancer Epidemiol Biomarkers Prev 18, 3000–3007.PubMedCrossRefGoogle Scholar
  45. 45.
    Padar, A., Sathyanarayana, U. G., Suzuki, M., Maruyama, R., Hsieh, J. T., Frenkel, E. P., Minna, J. D., and Gazdar, A. F. (2003) Inactivation of cyclin D2 gene in prostate cancers by aberrant promoter methylation, Clin Cancer Res 9, 4730–4734.PubMedGoogle Scholar
  46. 46.
    Aaltomaa, S., Eskelinen, M., and Lipponen, P. (1999) Expression of cyclin A and D proteins in prostate cancer and their relation to clinicopathological variables and patient survival, Prostate 38, 175–182.PubMedCrossRefGoogle Scholar
  47. 47.
    Wegiel, B., Bjartell, A., Tuomela, J., Dizeyi, N., Tinzl, M., Helczynski, L., Nilsson, E., Otterbein, L. E., Harkonen, P., and Persson, J. L. (2008) Multiple cellular mechanisms related to cyclin A1 in prostate cancer invasion and metastasis, J Natl Cancer Inst 100, 1022–1036.PubMedCrossRefGoogle Scholar
  48. 48.
    Shames, D. S., Girard, L., Gao, B., Sato, M., Lewis, C. M., Shivapurkar, N., Jiang, A., Perou, C. M., Kim, Y. H., Pollack, J. R., Fong, K. M., Lam, C. L., Wong, M., Shyr, Y., Nanda, R., Olopade, O. I., Gerald, W., Euhus, D. M., Shay, J. W., Gazdar, A. F., and Minna, J. D. (2006) A genome-wide screen for promoter methylation in lung cancer identifies novel methylation markers for multiple malignancies, PLoS Med 3, e486.PubMedCrossRefGoogle Scholar
  49. 49.
    Henrique, R., Costa, V. L., Cerveira, N., Carvalho, A. L., Hoque, M. O., Ribeiro, F. R., Oliveira, J., Teixeira, M. R., Sidransky, D., and Jeronimo, C. (2006) Hypermethylation of Cyclin D2 is associated with loss of mRNA expression and tumor development in prostate cancer, J Mol Med 84, 911–918.PubMedCrossRefGoogle Scholar
  50. 50.
    Henrique, R., Ribeiro, F. R., Fonseca, D., Hoque, M. O., Carvalho, A. L., Costa, V. L., Pinto, M., Oliveira, J., Teixeira, M. R., Sidransky, D., and Jeronimo, C. (2007) High promoter methylation levels of APC predict poor prognosis in sextant biopsies from prostate cancer patients, Clin Cancer Res 13, 6122–6129.CrossRefPubMedGoogle Scholar
  51. 51.
    Rosenbaum, E., Hoque, M. O., Cohen, Y., Zahurak, M., Eisenberger, M. A., Epstein, J. I., Partin, A. W., and Sidransky, D. (2005) Promoter hypermethylation as an independent prognostic factor for relapse in patients with prostate cancer following radical prostatectomy, Clin Cancer Res 11, 8321–8325.PubMedCrossRefGoogle Scholar
  52. 52.
    Mittag, F., Kuester, D., Vieth, M., Peters, B., Stolte, B., Roessner, A., and Schneider-Stock, R. (2006) DAPK promotor methylation is an early event in colorectal carcinogenesis, Cancer Lett 240, 69–75.PubMedCrossRefGoogle Scholar
  53. 53.
    Cohen, O., Feinstein, E., and Kimchi, A. (1997) DAP-kinase is a Ca2+/calmodulin-dependent, cytoskeletal-associated protein kinase, with cell death-inducing functions that depend on its catalytic activity, EMBO J 16, 998–1008.PubMedCrossRefGoogle Scholar
  54. 54.
    Chan, M. W., Chan, L. W., Tang, N. L., Tong, J. H., Lo, K. W., Lee, T. L., Cheung, H. Y., Wong, W. S., Chan, P. S., Lai, F. M., and To, K. F. (2002) Hypermethylation of multiple genes in tumor tissues and voided urine in urinary bladder cancer patients, Clin Cancer Res 8, 464–470.PubMedGoogle Scholar
  55. 55.
    Simpson, D. J., Clayton, R. N., and Farrell, W. E. (2002) Preferential loss of Death Associated Protein kinase expression in invasive pituitary tumours is associated with either CpG island methylation or homozygous deletion, Oncogene 21, 1217–1224.PubMedCrossRefGoogle Scholar
  56. 56.
    Yamanaka, M., Watanabe, M., Yamada, Y., Takagi, A., Murata, T., Takahashi, H., Suzuki, H., Ito, H., Tsukino, H., Katoh, T., Sugimura, Y., and Shiraishi, T. (2003) Altered methylation of multiple genes in carcinogenesis of the prostate, Int J Cancer 106, 382–387.PubMedCrossRefGoogle Scholar
  57. 57.
    Mishra, D. K., Chen, Z., Wu, Y., Sarkissyan, M., Koeffler, H. P., and Vadgama, J. V. (2010) Global methylation pattern of genes in androgen-sensitive and androgen-independent prostate cancer cells, Mol Cancer Ther 9, 33–45.PubMedCrossRefGoogle Scholar
  58. 58.
    Carvalho, J. R., Filipe, L., Costa, V. L., Ribeiro, F. R., Martins, A. T., Teixeira, M. R., Jeronimo, C., and Henrique, R. (2010) Detailed analysis of expression and promoter methylation status of apoptosis-related genes in prostate cancer, Apoptosis 15, 956–965.PubMedCrossRefGoogle Scholar
  59. 59.
    Michie, A. M., McCaig, A. M., Nakagawa, R., and Vukovic, M. (2010) Death-associated protein kinase (DAPK) and signal transduction: regulation in cancer, FEBS J 277, 74–80.PubMedCrossRefGoogle Scholar
  60. 60.
    Verri, C., Roz, L., Conte, D., Liloglou, T., Livio, A., Vesin, A., Fabbri, A., Andriani, F., Brambilla, C., Tavecchio, L., Calarco, G., Calabro, E., Mancini, A., Tosi, D., Bossi, P., Field, J. K., Brambilla, E., and Sozzi, G. (2009) Fragile histidine triad gene inactivation in lung cancer: the European Early Lung Cancer project, Am J Respir Crit Care Med 179, 396–401.PubMedCrossRefGoogle Scholar
  61. 61.
    Paulsson, K., An, Q., Moorman, A. V., Parker, H., Molloy, G., Davies, T., Griffiths, M., Ross, F. M., Irving, J., Harrison, C. J., Young, B. D., and Strefford, J. C. (2009) Methylation of tumour suppressor gene promoters in the presence and absence of transcriptional silencing in high hyperdiploid acute lymphoblastic leukaemia, Br J Haematol 144, 838–847.PubMedCrossRefGoogle Scholar
  62. 62.
    Hong, F. Z., Wang, B., Li, H. M., and Liew, C. T. (2005) (Hypermethylation of fragile histidine triad gene and 3p14 allelic deletion in ovarian carcinomas), Zhonghua Bing Li Xue Za Zhi 34, 257–261.PubMedGoogle Scholar
  63. 63.
    Goldberg, M., Rummelt, C., Laerm, A., Helmbold, P., Holbach, L. M., and Ballhausen, W. G. (2006) Epigenetic silencing contributes to frequent loss of the fragile histidine triad tumour suppressor in basal cell carcinomas, Br J Dermatol 155, 1154–1158.PubMedCrossRefGoogle Scholar
  64. 64.
    Neyaz, M. K., Kumar, R. S., Hussain, S., Naqvi, S. H., Kohaar, I., Thakur, N., Kashyap, V., Das, B. C., Husain, S. A., and Bharadwaj, M. (2008) Effect of aberrant promoter methylation of FHIT and RASSF1A genes on susceptibility to cervical cancer in a North Indian population, Biomarkers 13, 597–606.PubMedCrossRefGoogle Scholar
  65. 65.
    Leal, M. F., Lima, E. M., Silva, P. N., Assumpcao, P. P., Calcagno, D. Q., Payao, S. L., Burbano, R. R., and Smith, M. A. (2007) Promoter hypermethylation of CDH1, FHIT, MTAP and PLAGL1 in gastric adenocarcinoma in individuals from Northern Brazil, World J Gastroenterol 13, 2568–2574.PubMedGoogle Scholar
  66. 66.
    Kvasha, S., Gordiyuk, V., Kondratov, A., Ugryn, D., Zgonnyk, Y. M., Rynditch, A. V., and Vozianov, A. F. (2008) Hypermethylation of the 5′CpG island of the FHIT gene in clear cell renal carcinomas, Cancer Lett 265, 250–257.PubMedCrossRefGoogle Scholar
  67. 67.
    Kim, J. W., Cheng, Y., Liu, W., Li, T., Yegnasubramanian, S., Zheng, S. L., Xu, J., Isaacs, W. B., and Chang, B. L. (2009) Genetic and epigenetic inactivation of LPL gene in human prostate cancer, Int J Cancer 124, 734–738.PubMedCrossRefGoogle Scholar
  68. 68.
    Sard, L., Accornero, P., Tornielli, S., Delia, D., Bunone, G., Campiglio, M., Colombo, M. P., Gramegna, M., Croce, C. M., Pierotti, M. A., and Sozzi, G. (1999) The tumor-suppressor gene FHIT is involved in the regulation of apoptosis and in cell cycle control, Proc Natl Acad Sci USA 96, 8489–8492.PubMedCrossRefGoogle Scholar
  69. 69.
    Guo, Z., Johansson, S. L., Rhim Js., and Vishwanatha, J. K. (2000) Fragile histidine triad gene expression in primary prostate cancer and in an in vitro model, Prostate 43, 101–110.PubMedCrossRefGoogle Scholar
  70. 70.
    Latil, A., Bieche, I., Fournier, G., Cussenot, O., Pesche, S., and Lidereau, R. (1998) Molecular analysis of the FHIT gene in human prostate cancer, Oncogene 16, 1863–1868.PubMedCrossRefGoogle Scholar
  71. 71.
    Waha, A., Koch, A., Hartmann, W., Mack, H., Schramm, J., Sorensen, N., Berthold, F., Wiestler, O. D., and Pietsch, T. (2004) Analysis of HIC-1 methylation and transcription in human ependymomas, Int J Cancer 110, 542–549.PubMedCrossRefGoogle Scholar
  72. 72.
    Tam, K. F., Liu, V. W., Liu, S. S., Tsang, P. C., Cheung, A. N., Yip, A. M., and Ngan, H. Y. (2007) Methylation profile in benign, borderline and malignant ovarian tumors, J Cancer Res Clin Oncol 133, 331–341.PubMedCrossRefGoogle Scholar
  73. 73.
    Chopin, V., and Leprince, D. (2006) (Chromosome arm 17p13.3: could HIC1 be the one?), Med Sci (Paris) 22, 54–61.CrossRefGoogle Scholar
  74. 74.
    Chen, W. Y., Zeng, X., Carter, M. G., Morrell, C. N., Chiu Yen, R. W., Esteller, M., Watkins, D. N., Herman, J. G., Mankowski, J. L., and Baylin, S. B. (2003) Heterozygous disruption of Hic1 predisposes mice to a gender-dependent spectrum of malignant tumors, Nat Genet 33, 197–202.PubMedCrossRefGoogle Scholar
  75. 75.
    Chen, W., Cooper, T. K., Zahnow, C. A., Overholtzer, M., Zhao, Z., Ladanyi, M., Karp, J. E., Gokgoz, N., Wunder, J. S., Andrulis, I. L., Levine, A. J., Mankowski, J. L., and Baylin, S. B. (2004) Epigenetic and genetic loss of Hic1 function accentuates the role of p53 in tumorigenesis, Cancer Cell 6, 387–398.PubMedCrossRefGoogle Scholar
  76. 76.
    Kekeeva, T. V., Popova, O. P., Shegai, P. V., Alekseev, B., Adnreeva, I., Zaletaev, D. V., and Nemtsova, M. V. (2007) (Abberant methylation of p16, HIC1, N33 and GSTP1 genes in tumor epitelium and tumor-associated stromal cells of prostate cancer), Mol Biol (Mosk) 41, 79–85.CrossRefGoogle Scholar
  77. 77.
    Gallucci, M., Merola, R., Leonardo, C., De Carli, P., Farsetti, A., Sentinelli, S., Sperduti, I., Mottolese, M., Carlini, P., Vico, E., Simone, G., and Cianciulli, A. (2009) Genetic profile identification in clinically localized prostate carcinoma, Urol Oncol 27, 502–508.PubMedCrossRefGoogle Scholar
  78. 78.
    Kioussi, C., Briata, P., Baek, S. H., Rose, D. W., Hamblet, N. S., Herman, T., Ohgi, K. A., Lin, C., Gleiberman, A., Wang, J., Brault, V., Ruiz-Lozano, P., Nguyen, H. D., Kemler, R., Glass, C. K., Wynshaw-Boris, A., and Rosenfeld, M. G. (2002) Identification of a Wnt/Dvl/beta-Catenin - > Pitx2 pathway mediating cell-type-specific proliferation during development, Cell 111, 673–685.PubMedCrossRefGoogle Scholar
  79. 79.
    Maier, S., Nimmrich, I., Koenig, T., Eppenberger-Castori, S., Bohlmann, I., Paradiso, A., Spyratos, F., Thomssen, C., Mueller, V., Nahrig, J., Schittulli, F., Kates, R., Lesche, R., Schwope, I., Kluth, A., Marx, A., Martens, J. W., Foekens, J. A., Schmitt, M., and Harbeck, N. (2007) DNA-methylation of the homeodomain transcription factor PITX2 reliably predicts risk of distant disease recurrence in tamoxifen-treated, node-negative breast cancer patients-Technical and clinical validation in a multi-centre setting in collaboration with the European Organisation for Research and Treatment of Cancer (EORTC) PathoBiology group, Eur J Cancer 43, 1679–1686.PubMedCrossRefGoogle Scholar
  80. 80.
    Harbeck, N., Nimmrich, I., Hartmann, A., Ross, J. S., Cufer, T., Grutzmann, R., Kristiansen, G., Paradiso, A., Hartmann, O., Margossian, A., Martens, J., Schwope, I., Lukas, A., Muller, V., Milde-Langosch, K., Nahrig, J., Foekens, J., Maier, S., Schmitt, M., and Lesche, R. (2008) Multicenter study using paraffin-embedded tumor tissue testing PITX2 DNA methylation as a marker for outcome prediction in tamoxifen-treated, node-negative breast cancer patients, J Clin Oncol 26, 5036–5042.PubMedCrossRefGoogle Scholar
  81. 81.
    Nimmrich, I., Sieuwerts, A. M., Meijer-van Gelder, M. E., Schwope, I., Bolt-de Vries, J., Harbeck, N., Koenig, T., Hartmann, O., Kluth, A., Dietrich, D., Magdolen, V., Portengen, H., Look, M. P., Klijn, J. G., Lesche, R., Schmitt, M., Maier, S., Foekens, J. A., and Martens, J. W. (2008) DNA hypermethylation of PITX2 is a marker of poor prognosis in untreated lymph node-negative hormone receptor-positive breast cancer patients, Breast Cancer Res Treat 111, 429–437.PubMedCrossRefGoogle Scholar
  82. 82.
    Weiss, G., Cottrell, S., Distler, J., Schatz, P., Kristiansen, G., Ittmann, M., Haefliger, C., Lesche, R., Hartmann, A., Corman, J., and Wheeler, T. (2009) DNA methylation of the PITX2 gene promoter region is a strong independent prognostic marker of biochemical recurrence in patients with prostate cancer after radical prostatectomy, J Urol 181, 1678–1685.PubMedCrossRefGoogle Scholar
  83. 83.
    Banez, L. L., Sun, L., van Leenders, G. J., Wheeler, T. M., Bangma, C. H., Freedland, S. J., Ittmann, M. M., Lark, A. L., Madden, J. F., Hartman, A., Weiss, G., and Castanos-Velez, E. (2010) Multicenter clinical validation of PITX2 methylation as a prostate specific antigen recurrence predictor in patients with post-radical prostatectomy prostate cancer, J Urol 184, 149–156.PubMedCrossRefGoogle Scholar
  84. 84.
    Vanaja, D. K., Ehrich, M., Van den Boom, D., Cheville, J. C., Karnes, R. J., Tindall, D. J., Cantor, C. R., and Young, C. Y. (2009) Hypermethylation of genes for diagnosis and risk stratification of prostate cancer, Cancer Invest 27, 549–560.PubMedCrossRefGoogle Scholar
  85. 85.
    Hussain, S. P., and Harris, C. C. (2007) Inflammation and cancer: an ancient link with novel potentials, Int J Cancer 121, 2373–2380.PubMedCrossRefGoogle Scholar
  86. 86.
    Bastian, P. J., Ellinger, J., Wellmann, A., Wernert, N., Heukamp, L. C., Muller, S. C., and von Ruecker, A. (2005) Diagnostic and prognostic information in prostate cancer with the help of a small set of hypermethylated gene loci, Clin Cancer Res 11, 4097–4106.PubMedCrossRefGoogle Scholar
  87. 87.
    Bastian, P. J., Palapattu, G. S., Yegnasubra-manian, S., Rogers, C. G., Lin, X., Mangold, L. A., Trock, B., Eisenberger, M. A., Partin, A. W., and Nelson, W. G. (2008) CpG island hypermethylation profile in the serum of men with clinically localized and hormone refractory metastatic prostate cancer, J Urol 179, 529-534; discussion 534–525.Google Scholar
  88. 88.
    Ellinger, J., Bastian, P. J., Jurgan, T., Biermann, K., Kahl, P., Heukamp, L. C., Wernert, N., Muller, S. C., and von Ruecker, A. (2008) CpG island hypermethylation at multiple gene sites in diagnosis and prognosis of prostate cancer, Urology 71, 161–167.PubMedCrossRefGoogle Scholar
  89. 89.
    Bastian, P. J., Ellinger, J., Heukamp, L. C., Kahl, P., Muller, S. C., and von Rucker, A. (2007) Prognostic value of CpG island hypermethylation at PTGS2, RAR-beta, EDNRB, and other gene loci in patients undergoing radical prostatectomy, Eur Urol 51, 665-674; discussion 674.Google Scholar
  90. 90.
    Okegawa, T., Nutahara, K., and Higashihara, E. (2010) Association of circulating tumor cells with tumor-related methylated DNA in patients with hormone-refractory prostate cancer, Int J Urol 17, 466–475.PubMedCrossRefGoogle Scholar
  91. 91.
    Kuzmin, I., Gillespie, J. W., Protopopov, A., Geil, L., Dreijerink, K., Yang, Y., Vocke, C. D., Duh, F. M., Zabarovsky, E., Minna, J. D., Rhim, J. S., Emmert-Buck, M. R., Linehan, W. M., and Lerman, M. I. (2002) The RASSF1A tumor suppressor gene is inactivated in prostate tumors and suppresses growth of prostate carcinoma cells, Cancer Res 62, 3498–3502.PubMedGoogle Scholar
  92. 92.
    Liu, L., Yoon, J. H., Dammann, R., and Pfeifer, G. P. (2002) Frequent hypermethylation of the RASSF1A gene in prostate cancer, Oncogene 2111 6835–6840.PubMedCrossRefGoogle Scholar
  93. 93.
    Kang, G. H., Lee, S., Lee, H. J., and Hwang, K. S. (2004) Aberrant CpG island hypermethylation of multiple genes in prostate cancer and prostatic intraepithelial neoplasia, J Pathol 202, 233–240.PubMedCrossRefGoogle Scholar
  94. 94.
    Kawamoto, K., Okino, S. T., Place, R. F., Urakami, S., Hirata, H., Kikuno, N., Kawakami, T., Tanaka, Y., Pookot, D., Chen, Z., Majid, S., Enokida, H., Nakagawa, M., and Dahiya, R. (2007) Epigenetic modifications of RASSF1A gene through chromatin remodeling in prostate cancer, Clin Cancer Res 13, 2541–2548.PubMedCrossRefGoogle Scholar
  95. 95.
    Singal, R., Ferdinand, L., Reis, I. M., and Schlesselman, J. J. (2004) Methylation of multiple genes in prostate cancer and the relationship with clinicopathological features of disease, Oncol Rep 12, 631–637.PubMedGoogle Scholar
  96. 96.
    Aitchison, A., Warren, A., Neal, D., and Rabbitts, P. (2007) RASSF1A promoter methylation is frequently detected in both pre-malignant and non-malignant microdissected prostatic epithelial tissues, Prostate 67, 638–644.PubMedCrossRefGoogle Scholar
  97. 97.
    Srinivas, S. R., Gopal, E., Zhuang, L., Itagaki, S., Martin, P. M., Fei, Y. J., Ganapathy, V., and Prasad, P. D. (2005) Cloning and functional identification of slc5a12 as a sodium-coupled low-affinity transporter for monocarboxylates (SMCT2), Biochem J 392, 655–664.PubMedCrossRefGoogle Scholar
  98. 98.
    Kennedy, K. M., and Dewhirst, M. W. (2010) Tumor metabolism of lactate: the influence and therapeutic potential for MCT and CD147 regulation, Future Oncol 6, 127–148.PubMedCrossRefGoogle Scholar
  99. 99.
    Ganapathy, V., Thangaraju, M., Gopal, E., Martin, P. M., Itagaki, S., Miyauchi, S., and Prasad, P. D. (2008) Sodium-coupled monocarboxylate transporters in normal tissues and in cancer, AAPS J 10, 193–199.PubMedCrossRefGoogle Scholar
  100. 100.
    Schagdarsurengin, U., Gimm, O., Dralle, H., Hoang-Vu, C., and Dammann, R. (2006) CpG island methylation of tumor-related promoters occurs preferentially in undifferentiated carcinoma, Thyroid 16, 633–642.PubMedCrossRefGoogle Scholar
  101. 101.
    Li, H., Myeroff, L., Smiraglia, D., Romero, M. F., Pretlow, T. P., Kasturi, L., Lutterbaugh, J., Rerko, R. M., Casey, G., Issa, J. P., Willis, J., Willson, J. K., Plass, C., and Markowitz, S. D. (2003) SLC5A8, a sodium transporter, is a tumor suppressor gene silenced by methylation in human colon aberrant crypt foci and cancers, Proc Natl Acad Sci USA 100, 8412–8417.PubMedCrossRefGoogle Scholar
  102. 102.
    Park, J., Brena, RM., Gruidl, M., Zhou, J, Huang, T, Plass, C, and Tockman, MS. (2005) CpG island hypermethylation profiling of lung cancer using restriction landmark genomic scanning (RLGS) analysis., Cancer Biomarkers 1, 193–200.PubMedGoogle Scholar
  103. 103.
    Thangaraju, M., Gopal, E., Martin, P. M., Ananth, S., Smith, S. B., Prasad, P. D., Sterneck, E., and Ganapathy, V. (2006) SLC5A8 triggers tumor cell apoptosis through pyruvate-dependent inhibition of histone deacetylases, Cancer Res 66, 11560–11564.PubMedCrossRefGoogle Scholar
  104. 104.
    Dong, S. M., Lee, E. J., Jeon, E. S., Park, C. K., and Kim, K. M. (2005) Progressive methylation during the serrated neoplasia pathway of the colorectum, Mod Pathol 18, 170–178.PubMedCrossRefGoogle Scholar
  105. 105.
    Ganapathy, V., Gopal, E., Miyauchi, S., and Prasad, P. D. (2005) Biological functions of SLC5A8, a candidate tumour suppressor, Biochem Soc Trans 33, 237–240.PubMedCrossRefGoogle Scholar
  106. 106.
    Hong, C., Maunakea, A., Jun, P., Bollen, A. W., Hodgson, J. G., Goldenberg, D. D., Weiss, W. A., and Costello, J. F. (2005) Shared epigenetic mechanisms in human and mouse gliomas inactivate expression of the growth suppressor SLC5A8, Cancer Res 65, 3617–3623.PubMedCrossRefGoogle Scholar
  107. 107.
    Porra, V., Ferraro-Peyret, C., Durand, C., Selmi-Ruby, S., Giroud, H., Berger-Dutrieux, N., Decaussin, M., Peix, J. L., Bournaud, C., Orgiazzi, J., Borson-Chazot, F., Dante, R., and Rousset, B. (2005) Silencing of the tumor suppressor gene SLC5A8 is associated with BRAF mutations in classical papillary thyroid carcinomas, J Clin Endocrinol Metab 90, 3028–3035.PubMedCrossRefGoogle Scholar
  108. 108.
    Ueno, M., Toyota, M., Akino, K., Suzuki, H., Kusano, M., Satoh, A., Mita, H., Sasaki, Y., Nojima, M., Yanagihara, K., Hinoda, Y., Tokino, T., and Imai, K. (2004) Aberrant methylation and histone deacetylation associated with silencing of SLC5A8 in gastric cancer, Tumour Biol 25, 134–140.PubMedCrossRefGoogle Scholar
  109. 109.
    Hu, S., Liu, D., Tufano, R. P., Carson, K. A., Rosenbaum, E., Cohen, Y., Holt, E. H., Kiseljak-Vassiliades, K., Rhoden, K. J., Tolaney, S., Condouris, S., Tallini, G., Westra, W. H., Umbricht, C. B., Zeiger, M. A., Califano, J. A., Vasko, V., and Xing, M. (2006) Association of aberrant methylation of tumor suppressor genes with tumor aggressiveness and BRAF mutation in papillary thyroid cancer, Int J Cancer 119, 2322–2329.PubMedCrossRefGoogle Scholar
  110. 110.
    Park, J. Y., Helm, J. F., Zheng, W., Ly, Q. P., Hodul, P. J., Centeno, B. A., and Malafa, M. P. (2008) Silencing of the candidate tumor suppressor gene solute carrier family 5 member 8 (SLC5A8) in human pancreatic cancer, Pancreas 36, e32–39.PubMedCrossRefGoogle Scholar
  111. 111.
    Park, J. Y., Zheng, W., Kim, D., Cheng, J. Q., Kumar, N., Ahmad, N., and Pow-Sang, J. (2007) Candidate tumor suppressor gene SLC5A8 is frequently down-regulated by promoter hypermethylation in prostate tumor, Cancer Detect Prev 31, 359–365.PubMedCrossRefGoogle Scholar
  112. 112.
    Pinheiro, C., Reis, R. M., Ricardo, S., Longatto-Filho, A., Schmitt, F., and Baltazar, F. (2010) Expression of monocarboxylate transporters 1, 2, and 4 in human tumours and their association with CD147 and CD44, J Biomed Biotechnol 2010, 427694.PubMedCrossRefGoogle Scholar
  113. 113.
    Weihe, E., and Eiden, L. E. (2000) Chemical neuroanatomy of the vesicular amine transporters, FASEB J 14, 2435–2449.PubMedCrossRefGoogle Scholar
  114. 114.
    Kristiansen, G., Pilarsky, C., Wissmann, C., Kaiser, S., Bruemmendorf, T., Roepcke, S., Dahl, E., Hinzmann, B., Specht, T., Pervan, J., Stephan, C., Loening, S., Dietel, M., and Rosenthal, A. (2005) Expression profiling of microdissected matched prostate cancer samples reveals CD166/MEMD and CD24 as new prognostic markers for patient survival, J Pathol 205, 359–376.PubMedCrossRefGoogle Scholar
  115. 115.
    Sorensen, K. D., Wild, P. J., Mortezavi, A., Adolf, K., Torring, N., Heeboll, S., Ulhoi, B. P., Ottosen, P., Sulser, T., Hermanns, T., Moch, H., Borre, M., Orntoft, T. F., and Dyrskjot, L. (2009) Genetic and epigenetic SLC18A2 silencing in prostate cancer is an independent adverse predictor of biochemical recurrence after radical prostatectomy, Clin Cancer Res 15, 1400–1410.PubMedCrossRefGoogle Scholar
  116. 116.
    Chang, B. L., Liu, W., Sun, J., Dimitrov, L., Li, T., Turner, A. R., Zheng, S. L., Isaacs, W. B., and Xu, J. (2007) Integration of somatic deletion analysis of prostate cancers and germline linkage analysis of prostate cancer families reveals two small consensus regions for prostate cancer genes at 8p, Cancer Res 67, 4098–4103.PubMedCrossRefGoogle Scholar
  117. 117.
    Cheng, Y., Kim, J. W., Liu, W., Dunn, T. A., Luo, J., Loza, M. J., Kim, S. T., Zheng, S. L., Xu, J., Isaacs, W. B., and Chang, B. L. (2009) Genetic and epigenetic inactivation of TNFRSF10C in human prostate cancer, Prostate 69, 327–335.PubMedCrossRefGoogle Scholar
  118. 118.
    Shivapurkar, N., Toyooka, S., Toyooka, K. O., Reddy, J., Miyajima, K., Suzuki, M., Shigematsu, H., Takahashi, T., Parikh, G., Pass, H. I., Chaudhary, P. M., and Gazdar, A. F. (2004) Aberrant methylation of trail decoy receptor genes is frequent in multiple tumor types, Int J Cancer 109, 786–792.PubMedCrossRefGoogle Scholar
  119. 119.
    van Noesel, M. M., van Bezouw, S., Salomons, G. S., Voute, P. A., Pieters, R., Baylin, S. B., Herman, J. G., and Versteeg, R. (2002) Tumor-specific down-regulation of the tumor necrosis factor-related apoptosis-inducing ligand decoy receptors DcR1 and DcR2 is associated with dense promoter hypermethylation, Cancer Res 62, 2157–2161.PubMedGoogle Scholar
  120. 120.
    Hornstein, M., Hoffmann, M. J., Alexa, A., Yamanaka, M., Muller, M., Jung, V., Rahnenfuhrer, J., and Schulz, W. A. (2008) Protein phosphatase and TRAIL receptor genes as new candidate tumor genes on chromosome 8p in prostate cancer, Cancer Genomics Proteomics 5, 123–136.PubMedGoogle Scholar
  121. 121.
    Cho, N. Y., Kim, J. H., Moon, K. C., and Kang, G. H. (2009) Genomic hypomethylation and CpG island hypermethylation in prostatic intraepithelial neoplasm, Virchows Arch 454, 17–23.PubMedCrossRefGoogle Scholar
  122. 122.
    Cho, N. Y., Kim, B. H., Choi, M., Yoo, E. J., Moon, K. C., Cho, Y. M., Kim, D., and Kang, G. H. (2007) Hypermethylation of CpG island loci and hypomethylation of LINE-1 and Alu repeats in prostate adenocarcinoma and their relationship to clinicopathological features, J Pathol 211, 269–277.PubMedCrossRefGoogle Scholar
  123. 123.
    Barnabas, N., Xu, L., Savera, A., Hou, Z., and Barrack, E. R. (2010) Chromosome 8 markers of metastatic prostate cancer in African American men: Gain of the MIR151 gene and loss of the NKX3-1 gene, Prostate.Google Scholar
  124. 124.
    Ju, J. H., Maeng, J. S., Zemedkun, M., Ahronovitz, N., Mack, J. W., Ferretti, J. A., Gelmann, E. P., and Gruschus, J. M. (2006) Physical and functional interactions between the prostate suppressor homeoprotein NKX3.1 and serum response factor, J Mol Biol 360, 989–999.PubMedCrossRefGoogle Scholar
  125. 125.
    Shen, M. M., and Abate-Shen, C. (2010) Molecular genetics of prostate cancer: new prospects for old challenges, Genes Dev 24, 1967–2000.PubMedCrossRefGoogle Scholar
  126. 126.
    Ouyang, X., DeWeese, T. L., Nelson, W. G., and Abate-Shen, C. (2005) Loss-of-function of Nkx3.1 promotes increased oxidative damage in prostate carcinogenesis, Cancer Res 65, 6773–6779.PubMedCrossRefGoogle Scholar
  127. 127.
    Bowen, C., Bubendorf, L., Voeller, H. J., Slack, R., Willi, N., Sauter, G., Gasser, T. C., Koivisto, P., Lack, E. E., Kononen, J., Kallioniemi, O. P., and Gelmann, E. P. (2000) Loss of NKX3.1 expression in human prostate cancers correlates with tumor progression, Cancer Res 60, 6111–6115.PubMedGoogle Scholar
  128. 128.
    Gurel, B., Ali, T. Z., Montgomery, E. A., Begum, S., Hicks, J., Goggins, M., Eberhart, C. G., Clark, D. P., Bieberich, C. J., Epstein, J. I., and De Marzo, A. M. (2010) NKX3.1 as a marker of prostatic origin in metastatic tumors, Am J Surg Pathol 34, 1097–1105.PubMedCrossRefGoogle Scholar
  129. 129.
    Asatiani, E., Huang, W. X., Wang, A., Rodriguez Ortner, E., Cavalli, L. R., Haddad, B. R., and Gelmann, E. P. (2005) Deletion, methylation, and expression of the NKX3.1 suppressor gene in primary human prostate cancer, Cancer Res 65, 1164–1173.PubMedCrossRefGoogle Scholar
  130. 130.
    Lind, G. E., Skotheim, R. I., Fraga, M. F., Abeler, V. M., Henrique, R., Saatcioglu, F., Esteller, M., Teixeira, M. R., and Lothe, R. A. (2005) The loss of NKX3.1 expression in testicular-and prostate-cancers is not caused by promoter hypermethylation, Mol Cancer 4, 8.PubMedCrossRefGoogle Scholar
  131. 131.
    Chung, W., Kwabi-Addo, B., Ittmann, M., Jelinek, J., Shen, L., Yu, Y., and Issa, J. P. (2008) Identification of novel tumor markers in prostate, colon and breast cancer by unbiased methylation profiling, PLoS One 3, e2079.PubMedCrossRefGoogle Scholar
  132. 132.
    Kwabi-Addo, B., Wang, S., Chung, W., Jelinek, J., Patierno, S. R., Wang, B. D., Andrawis, R., Lee, N. H., Apprey, V., Issa, J. P., and Ittmann, M. (2010) Identification of differentially methylated genes in normal prostate tissues from African American and Caucasian men, Clin Cancer Res 16, 3539–3547.PubMedCrossRefGoogle Scholar
  133. 133.
    Reibenwein, J., Pils, D., Horak, P., Tomicek, B., Goldner, G., Worel, N., Elandt, K., and Krainer, M. (2007) Promoter hypermethylation of GSTP1, AR, and 14-3-3sigma in serum of prostate cancer patients and its clinical relevance, Prostate 67, 427–432.PubMedCrossRefGoogle Scholar
  134. 134.
    Lodygin, D., and Hermeking, H. (2005) The role of epigenetic inactivation of 14-3-3sigma in human cancer, Cell Res 15, 237–246.PubMedCrossRefGoogle Scholar
  135. 135.
    Henrique, R., Jeronimo, C., Hoque, M. O., Carvalho, A. L., Oliveira, J., Teixeira, M. R., Lopes, C., and Sidransky, D. (2005) Frequent 14-3-3 sigma promoter methylation in benign and malignant prostate lesions, DNA Cell Biol 24, 264–269.PubMedCrossRefGoogle Scholar
  136. 136.
    Henderson, B. E., Ross, R. K., Pike, M. C., and Casagrande, J. T. (1982) Endogenous hormones as a major factor in human cancer, Cancer Res 42, 3232–3239.PubMedGoogle Scholar
  137. 137.
    Henderson, B. E., Ross, R. K., and Pike, M. C. (1991) Toward the primary prevention of cancer, Science 254, 1131–1138.PubMedCrossRefGoogle Scholar
  138. 138.
    Ellem, S. J., and Risbridger, G. P. (2010) Aromatase and regulating the estrogen:androgen ratio in the prostate gland, J Steroid Biochem Mol Biol 118, 246-251.PubMedCrossRefGoogle Scholar
  139. 139.
    Wang, Q., Li, W., Zhang, Y., Yuan, X., Xu, K., Yu, J., Chen, Z., Beroukhim, R., Wang, H., Lupien, M., Wu, T., Regan, M. M., Meyer, C. A., Carroll, J. S., Manrai, A. K., Janne, O. A., Balk, S. P., Mehra, R., Han, B., Chinnaiyan, A. M., Rubin, M. A., True, L., Fiorentino, M., Fiore, C., Loda, M., Kantoff, P. W., Liu, X. S., and Brown, M. (2009) Androgen receptor regulates a distinct transcription program in androgen-independent prostate cancer, Cell 138, 245p256.PubMedCrossRefGoogle Scholar
  140. 140.
    Eder, I. E., Culig, Z., Ramoner, R., Thurnher, M., Putz, T., Nessler-Menardi, C., Tiefenthaler, M., Bartsch, G., and Klocker, H. (2000) Inhibition of LncaP prostate cancer cells by means of androgen receptor antisense oligonucleotides, Cancer Gene Ther 7, 997–1007.PubMedCrossRefGoogle Scholar
  141. 141.
    Mitchell, S. H., Zhu, W., and Young, C. Y. (1999) Resveratrol inhibits the expression and function of the androgen receptor in LNCaP prostate cancer cells, Cancer Res 59, 5892–5895.PubMedGoogle Scholar
  142. 142.
    Tong, Q., Zeng, F., Lin, C., Zhao, J., and Lu, G. (2003) Growth inhibiting effects of antisense eukaryotic expression vector of proliferating cell nuclear antigen gene on human bladder cancer cells, Chin Med J (Engl) 116, 1203–1206.Google Scholar
  143. 143.
    Heisler, L. E., Evangelou, A., Lew, A. M., Trachtenberg, J., Elsholtz, H. P., and Brown, T. J. (1997) Androgen-dependent cell cycle arrest and apoptotic death in PC-3 prostatic cell cultures expressing a full-length human androgen receptor, Mol Cell Endocrinol 126, 59–73.PubMedCrossRefGoogle Scholar
  144. 144.
    Grossmann, M. E., Huang, H., and Tindall, D. J. (2001) Androgen receptor signaling in androgen-refractory prostate cancer, J Natl Cancer Inst 93, 1687–1697.PubMedCrossRefGoogle Scholar
  145. 145.
    Jarrard, D. F., Kinoshita, H., Shi, Y., Sandefur, C., Hoff, D., Meisner, L. F., Chang, C., Herman, J. G., Isaacs, W. B., and Nassif, N. (1998) Methylation of the androgen receptor promoter CpG island is associated with loss of androgen receptor expression in prostate cancer cells, Cancer Res 58, 5310–5314.PubMedGoogle Scholar
  146. 146.
    Kinoshita, H., Shi, Y., Sandefur, C., Meisner, L. F., Chang, C., Choon, A., Reznikoff, C. R., Bova, G. S., Friedl, A., and Jarrard, D. F. (2000) Methylation of the androgen receptor minimal promoter silences transcription in human prostate cancer, Cancer Res 60, 3623–3630.PubMedGoogle Scholar
  147. 147.
    Sasaki, M., Tanaka, Y., Perinchery, G., Dharia, A., Kotcherguina, I., Fujimoto, S., and Dahiya, R. (2002) Methylation and inactivation of estrogen, progesterone, and androgen receptors in prostate cancer, J Natl Cancer Inst 94, 384–390.PubMedCrossRefGoogle Scholar
  148. 148.
    Nakayama, T., Watanabe, M., Suzuki, H., Toyota, M., Sekita, N., Hirokawa, Y., Mizokami, A., Ito, H., Yatani, R., and Shiraishi, T. (2000) Epigenetic regulation of androgen receptor gene expression in human prostate cancers, Lab Invest 80, 1789–1796.PubMedCrossRefGoogle Scholar
  149. 149.
    Schayek, H., Bentov, I., Sun, S., Plymate, S. R., and Werner, H. (2010) Progression to metastatic stage in a cellular model of prostate cancer is associated with methylation of the androgen receptor gene and transcriptional suppression of the insulin-like growth factor-I receptor gene, Exp Cell Res 316, 1479–1488.PubMedCrossRefGoogle Scholar
  150. 150.
    Bosland, M. C. (2005) The role of estrogens in prostate carcinogenesis: a rationale for chemoprevention, Rev Urol 7 Suppl 3, S4–S10.PubMedGoogle Scholar
  151. 151.
    Li, L. C., Okino, S. T., and Dahiya, R. (2004) DNA methylation in prostate cancer, Biochim Biophys Acta 1704, 87–102.PubMedGoogle Scholar
  152. 152.
    Hobisch, A., Hittmair, A., Daxenbichler, G., Wille, S., Radmayr, C., Hobisch-Hagen, P., Bartsch, G., Klocker, H., and Culig, Z. (1997) Metastatic lesions from prostate cancer do not express oestrogen and progesterone receptors, J Pathol 182, 356–361.PubMedCrossRefGoogle Scholar
  153. 153.
    Horvath, L. G., Henshall, S. M., Lee, C. S., Head, D. R., Quinn, D. I., Makela, S., Delprado, W., Golovsky, D., Brenner, P. C., O’Neill, G., Kooner, R., Stricker, P. D., Grygiel, J. J., Gustafsson, J. A., and Sutherland, R. L. (2001) Frequent loss of estrogen receptor-beta expression in prostate cancer, Cancer Res 61, 5331–5335.PubMedGoogle Scholar
  154. 154.
    Zhu, X., Leav, I., Leung, Y. K., Wu, M., Liu, Q., Gao, Y., McNeal, J. E., and Ho, S. M. (2004) Dynamic regulation of estrogen receptor-beta expression by DNA methylation during prostate cancer development and metastasis, Am J Pathol 164, 2003–2012.PubMedCrossRefGoogle Scholar
  155. 155.
    Zhang, X., Leung, Y. K., and Ho, S. M. (2007) AP-2 regulates the transcription of estrogen receptor (ER)-beta by acting through a methylation hotspot of the 0N promoter in prostate cancer cells, Oncogene 26, 7346–7354.PubMedCrossRefGoogle Scholar
  156. 156.
    Konishi, N., Nakaoka, S., Hiasa, Y., Kitahori, Y., Ohshima, M., Samma, S., and Okajima, E. (1993) Immunohistochemical evaluation of estrogen receptor status in benign prostatic hypertrophy and in prostate carcinoma and the relationship to efficacy of endocrine therapy, Oncology 50, 259–263.PubMedCrossRefGoogle Scholar
  157. 157.
    Moriyama-Gonda, N., Shiina, H., Terashima, M., Satoh, K., and Igawa, M. (2008) Rationale and clinical implication of combined chemotherapy with cisplatin and oestrogen in prostate cancer: primary evidence based on methylation analysis of oestrogen receptor-alpha, BJU Int 101, 485–491.PubMedGoogle Scholar
  158. 158.
    Li, L. C., Chui, R., Nakajima, K., Oh, B. R., Au, H. C., and Dahiya, R. (2000) Frequent methylation of estrogen receptor in prostate cancer: correlation with tumor progression, Cancer Res 60, 702–706.PubMedGoogle Scholar
  159. 159.
    Leav, I., Lau, K. M., Adams, J. Y., McNeal, J. E., Taplin, M. E., Wang, J., Singh, H., and Ho, S. M. (2001) Comparative studies of the estrogen receptors beta and alpha and the androgen receptor in normal human prostate glands, dysplasia, and in primary and metastatic carcinoma, Am J Pathol 159, 79–92.PubMedCrossRefGoogle Scholar
  160. 160.
    Yao, Q., He, X. S., Zhang, J. M., and He, J. (2006) (Promotor hypermethylation of E-cadherin, p16 and estrogen receptor in prostate carcinoma), Zhonghua Nan Ke Xue 12, 28–31.PubMedGoogle Scholar
  161. 161.
    Nojima, D., Li, L. C., Dharia, A., Perinchery, G., Ribeiro-Filho, L., Yen, T. S., and Dahiya, R. (2001) CpG hypermethylation of the promoter region inactivates the estrogen receptor-beta gene in patients with prostate carcinoma, Cancer 92, 2076–2083.PubMedCrossRefGoogle Scholar
  162. 162.
    Hayashi, K., Yokozaki, H., Naka, K., Yasui, W., Lotan, R., and Tahara, E. (2001) Overexpression of retinoic acid receptor beta induces growth arrest and apoptosis in oral cancer cell lines, Jpn J Cancer Res 92, 42–50.PubMedCrossRefGoogle Scholar
  163. 163.
    Nakayama, T., Watanabe, M., Yamanaka, M., Hirokawa, Y., Suzuki, H., Ito, H., Yatani, R., and Shiraishi, T. (2001) The role of epigenetic modifications in retinoic acid receptor beta2 gene expression in human prostate cancers, Lab Invest 81, 1049–1057.PubMedCrossRefGoogle Scholar
  164. 164.
    Zhang, J., Liu, L., and Pfeifer, G. P. (2004) Methylation of the retinoid response gene TIG1 in prostate cancer correlates with methylation of the retinoic acid receptor beta gene, Oncogene 23, 2241–2249.PubMedCrossRefGoogle Scholar
  165. 165.
    Zon, G., Barker, M. A., Kaur, P., Groshen, S., Jones, L. W., Imam, S. A., and Boyd, V. L. (2009) Formamide as a denaturant for bisulfite conversion of genomic DNA: Bisulfite sequencing of the GSTPi and RARbeta2 genes of 43 formalin-fixed paraffin-embedded prostate cancer specimens, Anal Biochem 392, 117–125.PubMedCrossRefGoogle Scholar
  166. 166.
    Roupret, M., Hupertan, V., Catto, J. W., Yates, D. R., Rehman, I., Proctor, L. M., Phillips, J., Meuth, M., Cussenot, O., and Hamdy, F. C. (2008) Promoter hypermethylation in circulating blood cells identifies prostate cancer progression, Int J Cancer 122, 952–956.PubMedCrossRefGoogle Scholar
  167. 167.
    Henrique, R., and Jeronimo, C. (2004) Molecular detection of prostate cancer: a role for GSTP1 hypermethylation, Eur Urol 46, 660-669; discussion 669.Google Scholar
  168. 168.
    Nelson, C. P., Kidd, L. C., Sauvageot, J., Isaacs, W. B., De Marzo, A. M., Groopman, J. D., Nelson, W. G., and Kensler, T. W. (2001) Protection against 2-hydroxyamino-1-methyl-6-phenylimidazo(4,5-b)pyridine cytotoxicity and DNA adduct formation in human prostate by glutathione S-transferase P1, Cancer Res 61, 103–109.PubMedGoogle Scholar
  169. 169.
    Lee, W. H., Morton, R. A., Epstein, J. I., Brooks, J. D., Campbell, P. A., Bova, G. S., Hsieh, W. S., Isaacs, W. B., and Nelson, W. G. (1994) Cytidine methylation of regulatory sequences near the pi-class glutathione S-transferase gene accompanies human prostatic carcinogenesis, Proc Natl Acad Sci USA 91, 11733–11737.PubMedCrossRefGoogle Scholar
  170. 170.
    Harden, S. V., Guo, Z., Epstein, J. I., and Sidransky, D. (2003) Quantitative GSTP1 methylation clearly distinguishes benign prostatic tissue and limited prostate adenocarcinoma, J Urol 169, 1138–1142.PubMedCrossRefGoogle Scholar
  171. 171.
    Cairns, P., Esteller, M., Herman, J. G., Schoenberg, M., Jeronimo, C., Sanchez-Cespedes, M., Chow, N. H., Grasso, M., Wu, L., Westra, W. B., and Sidransky, D. (2001) Molecular detection of prostate cancer in urine by GSTP1 hypermethylation, Clin Cancer Res 7, 2727–2730.PubMedGoogle Scholar
  172. 172.
    Lee, W. H., Isaacs, W. B., Bova, G. S., and Nelson, W. G. (1997) CG island methylation changes near the GSTP1 gene in prostatic carcinoma cells detected using the polymerase chain reaction: a new prostate cancer biomarker, Cancer Epidemiol Biomarkers Prev 6, 443–450.PubMedGoogle Scholar
  173. 173.
    Santourlidis, S., Florl, A., Ackermann, R., Wirtz, H. C., and Schulz, W. A. (1999) High frequency of alterations in DNA methylation in adenocarcinoma of the prostate, Prostate 39, 166–174.PubMedCrossRefGoogle Scholar
  174. 174.
    Goessl, C., Krause, H., Muller, M., Heicappell, R., Schrader, M., Sachsinger, J., and Miller, K. (2000) Fluorescent methylation-specific polymerase chain reaction for DNA-based detection of prostate cancer in bodily fluids, Cancer Res 60, 5941–5945.PubMedGoogle Scholar
  175. 175.
    Jeronimo, C., Usadel, H., Henrique, R., Oliveira, J., Lopes, C., Nelson, W. G., and Sidransky, D. (2001) Quantitation of GSTP1 methylation in non-neoplastic prostatic tissue and organ-confined prostate adenocarcinoma, J Natl Cancer Inst 93, 1747–1752.PubMedCrossRefGoogle Scholar
  176. 176.
    Gonzalgo, M. L., Pavlovich, C. P., Lee, S. M., and Nelson, W. G. (2003) Prostate cancer detection by GSTP1 methylation analysis of postbiopsy urine specimens, Clin Cancer Res 9, 2673–2677.PubMedGoogle Scholar
  177. 177.
    Jeronimo, C., Varzim, G., Henrique, R., Oliveira, J., Bento, M. J., Silva, C., Lopes, C., and Sidransky, D. (2002) I105V polymorphism and promoter methylation of the GSTP1 gene in prostate adenocarcinoma, Cancer Epidemiol Biomarkers Prev 11, 445–450.PubMedGoogle Scholar
  178. 178.
    Woodson, K., Hayes, R., Wideroff, L., Villaruz, L., and Tangrea, J. (2003) Hypermethylation of GSTP1, CD44, and E-cadherin genes in prostate cancer among US Blacks and Whites, Prostate 55, 199–205.PubMedCrossRefGoogle Scholar
  179. 179.
    Kollermann, J., Muller, M., Goessl, C., Krause, H., Helpap, B., Pantel, K., and Miller, K. (2003) Methylation-specific PCR for DNA-based detection of occult tumor cells in lymph nodes of prostate cancer patients, Eur Urol 44, 533–538.PubMedCrossRefGoogle Scholar
  180. 180.
    Payne, S. R., Serth, J., Schostak, M., Kamradt, J., Strauss, A., Thelen, P., Model, F., Day, J. K., Liebenberg, V., Morotti, A., Yamamura, S., Lograsso, J., Sledziewski, A., and Semjonow, A. (2009) DNA methylation biomarkers of prostate cancer: confirmation of candidates and evidence urine is the most sensitive body fluid for non-invasive detection, Prostate 69, 1257–1269.PubMedCrossRefGoogle Scholar
  181. 181.
    Suh, C. I., Shanafelt, T., May, D. J., Shroyer, K. R., Bobak, J. B., Crawford, E. D., Miller, G. J., Markham, N., and Glode, L. M. (2000) Comparison of telomerase activity and GSTP1 promoter methylation in ejaculate as potential screening tests for prostate cancer, Mol Cell Probes 14, 211–217.PubMedCrossRefGoogle Scholar
  182. 182.
    Goessl, C., Muller, M., Heicappell, R., Krause, H., and Miller, K. (2001) DNA-based detection of prostate cancer in blood, urine, and ejaculates, Ann N Y Acad Sci 945, 51–58.PubMedCrossRefGoogle Scholar
  183. 183.
    Ellinger, J., Haan, K., Heukamp, L. C., Kahl, P., Buttner, R., Muller, S. C., von Ruecker, A., and Bastian, P. J. (2008) CpG island hypermethylation in cell-free serum DNA identifies patients with localized prostate cancer, Prostate 68, 42–49.PubMedCrossRefGoogle Scholar
  184. 184.
    Vener, T., Derecho, C., Baden, J., Wang, H., Rajpurohit, Y., Skelton, J., Mehrotra, J., Varde, S., Chowdary, D., Stallings, W., Leibovich, B., Robin, H., Pelzer, A., Schafer, G., Auprich, M., Mannweiler, S., Amersdorfer, P., and Mazumder, A. (2008) Development of a multiplexed urine assay for prostate cancer diagnosis, Clin Chem 54, 874–882.PubMedCrossRefGoogle Scholar
  185. 185.
    Pasquali, D., Rossi, V., Bellastella, G., Bellastella, A., and Sinisi, A. A. (2006) Natural and synthetic retinoids in prostate cancer, Curr Pharm Des 12, 1923–1929.PubMedCrossRefGoogle Scholar
  186. 186.
    Bushue, N., and Wan, Y. J. (2010) Retinoid pathway and cancer therapeutics, Adv Drug Deliv Rev.Google Scholar
  187. 187.
    Murphy, T. M., Perry, A. S., and Lawler, M. (2008) The emergence of DNA methylation as a key modulator of aberrant cell death in prostate cancer, Endocr Relat Cancer 15, 11–25.PubMedCrossRefGoogle Scholar
  188. 188.
    Esteller, M., Guo, M., Moreno, V., Peinado, M. A., Capella, G., Galm, O., Baylin, S. B., and Herman, J. G. (2002) Hypermethylation-associated Inactivation of the Cellular Retinol-Binding-Protein 1 Gene in Human Cancer, Cancer Res 62, 5902–5905.PubMedGoogle Scholar
  189. 189.
    Jeronimo, C., Henrique, R., Oliveira, J., Lobo, F., Pais, I., Teixeira, M. R., and Lopes, C. (2004) Aberrant cellular retinol binding protein 1 (CRBP1) gene expression and promoter methylation in prostate cancer, J Clin Pathol 57, 872–876.PubMedCrossRefGoogle Scholar
  190. 190.
    Suzuki, M., Shigematsu, H., Shivapurkar, N., Reddy, J., Miyajima, K., Takahashi, T., Gazdar, A. F., and Frenkel, E. P. (2006) Methylation of apoptosis related genes in the pathogenesis and prognosis of prostate cancer, Cancer Lett 242, 222–230.PubMedCrossRefGoogle Scholar
  191. 191.
    Enokida, H., Shiina, H., Igawa, M., Ogishima, T., Kawakami, T., Bassett, W. W., Anast, J. W., Li, L. C., Urakami, S., Terashima, M., Verma, M., Kawahara, M., Nakagawa, M., Kane, C. J., Carroll, P. R., and Dahiya, R. (2004) CpG hypermethylation of MDR1 gene contributes to the pathogenesis and progression of human prostate cancer, Cancer Res 64, 5956–5962.PubMedCrossRefGoogle Scholar
  192. 192.
    Enokida, H., Shiina, H., Urakami, S., Igawa, M., Ogishima, T., Li, L. C., Kawahara, M., Nakagawa, M., Kane, C. J., Carroll, P. R., and Dahiya, R. (2005) Multigene methylation analysis for detection and staging of prostate cancer, Clin Cancer Res 11, 6582–6588.PubMedCrossRefGoogle Scholar
  193. 193.
    Knight, L. J., Burrage, J., Bujac, S. R., Haggerty, C., Graham, A., Gibson, N. J., Ellison, G., Growcott, J. W., Brooks, A. N., Hughes, A. M., Xinarianos, G., Nikolaidis, G., Field, J. K., and Liloglou, T. (2009) Epigenetic silencing of the endothelin-B receptor gene in non-small cell lung cancer, Int J Oncol 34, 465–471.PubMedGoogle Scholar
  194. 194.
    Nelson, J. B., Lee, W. H., Nguyen, S. H., Jarrard, D. F., Brooks, J. D., Magnuson, S. R., Opgenorth, T. J., Nelson, W. G., and Bova, G. S. (1997) Methylation of the 5′ CpG island of the endothelin B receptor gene is common in human prostate cancer, Cancer Res 57, 35–37.PubMedGoogle Scholar
  195. 195.
    Rogers, C. G., Gonzalgo, M. L., Yan, G., Bastian, P. J., Chan, D. Y., Nelson, W. G., and Pavlovich, C. P. (2006) High concordance of gene methylation in post-digital rectal examination and post-biopsy urine samples for prostate cancer detection, J Urol 176, 2280–2284.PubMedCrossRefGoogle Scholar
  196. 196.
    Jeronimo, C., Henrique, R., Campos, P. F., Oliveira, J., Caballero, O. L., Lopes, C., and Sidransky, D. (2003) Endothelin B receptor gene hypermethylation in prostate adenocarcinoma, J Clin Pathol 56, 52–55.PubMedCrossRefGoogle Scholar
  197. 197.
    Adams, R. H. (2002) Vascular patterning by Eph receptor tyrosine kinases and ephrins, Semin Cell Dev Biol 13, 55–60.PubMedCrossRefGoogle Scholar
  198. 198.
    Guan, M., Xu, C., Zhang, F., and Ye, C. (2009) Aberrant methylation of EphA7 in human prostate cancer and its relation to clinicopathologic features, Int J Cancer 124, 88–94.PubMedCrossRefGoogle Scholar
  199. 199.
    Katoh, M. (2006) Comparative integromics on Eph family, Int J Oncol 28, 1243–1247.PubMedGoogle Scholar
  200. 200.
    Oudes, A. J., Roach, J. C., Walashek, L. S., Eichner, L. J., True, L. D., Vessella, R. L., and Liu, A. Y. (2005) Application of Affymetrix array and Massively Parallel Signature Sequencing for identification of genes involved in prostate cancer progression, BMC Cancer 5, 86.PubMedCrossRefGoogle Scholar
  201. 201.
    Wang, J., Kataoka, H., Suzuki, M., Sato, N., Nakamura, R., Tao, H., Maruyama, K., Isogaki, J., Kanaoka, S., Ihara, M., Tanaka, M., Kanamori, M., Nakamura, T., Shinmura, K., and Sugimura, H. (2005) Downregulation of EphA7 by hypermethylation in colorectal cancer, Oncogene 24, 5637–5647.PubMedCrossRefGoogle Scholar
  202. 202.
    Youssef, E. M., Chen, X. Q., Higuchi, E., Kondo, Y., Garcia-Manero, G., Lotan, R., and Issa, J. P. (2004) Hypermethylation and silencing of the putative tumor suppressor Tazarotene-induced gene 1 in human cancers, Cancer Res 64, 2411–2417.PubMedCrossRefGoogle Scholar
  203. 203.
    Lotan, R. (2002) Is TIG1 a new tumor suppressor in prostate cancer?, J Natl Cancer Inst 94, 469–470.PubMedCrossRefGoogle Scholar
  204. 204.
    Tokumaru, Y., Harden, S. V., Sun, D. I., Yamashita, K., Epstein, J. I., and Sidransky, D. (2004) Optimal use of a panel of methylation markers with GSTP1 hypermethylation in the diagnosis of prostate adenocarcinoma, Clin Cancer Res 10, 5518–5522.PubMedCrossRefGoogle Scholar
  205. 205.
    Tokumaru, Y., Sun, D. I., Nomoto, S., Yamashita, K., and Sidransky, D. (2003) Re: Is TIG1 a new tumor suppressor in prostate cancer?, J Natl Cancer Inst 95, 919–920.PubMedCrossRefGoogle Scholar
  206. 206.
    Vasiliou, V., Pappa, A., and Estey, T. (2004) Role of human aldehyde dehydrogenases in endobiotic and xenobiotic metabolism, Drug Metab Rev 36, 279–299.PubMedCrossRefGoogle Scholar
  207. 207.
    Pasquali, D., Thaller, C., and Eichele, G. (1996) Abnormal level of retinoic acid in prostate cancer tissues, J Clin Endocrinol Metab 81, 2186–2191.PubMedCrossRefGoogle Scholar
  208. 208.
    Touma, S. E., Perner, S., Rubin, M. A., Nanus, D. M., and Gudas, L. J. (2009) Retinoid metabolism and ALDH1A2 (RALDH2) expression are altered in the transgenic adenocarcinoma mouse prostate model, Biochem Pharmacol 78, 1127–1138.PubMedCrossRefGoogle Scholar
  209. 209.
    Kim, H., Lapointe, J., Kaygusuz, G., Ong, D. E., Li, C., van de Rijn, M., Brooks, J. D., and Pollack, J. R. (2005) The retinoic acid synthesis gene ALDH1a2 is a candidate tumor suppressor in prostate cancer, Cancer Res 65, 8118–8124.PubMedCrossRefGoogle Scholar
  210. 210.
    Trasino, S. E., Harrison, E. H., and Wang, T. T. (2007) Androgen regulation of aldehyde dehydrogenase 1A3 (ALDH1A3) in the androgen-responsive human prostate cancer cell line LNCaP, Exp Biol Med (Maywood) 232, 762–771.Google Scholar
  211. 211.
    Lin, J., Haffner, M. C., Zhang, Y., Lee, B. H., Brennen, W. N., Britton, J., Kachhap, S. K., Shim, J. S., Liu, J. O., Nelson, W. G., Yegnasubra-manian, S., and Carducci, M. A. (2010) Disulfiram is a DNA demethylating agent and inhibits prostate cancer cell growth, Prostate.Google Scholar
  212. 212.
    Costa, V. L., Henrique, R., Ribeiro, F. R., Carvalho, J. R., Oliveira, J., Lobo, F., Teixeira, M. R., and Jeronimo, C. (2010) Epigenetic regulation of Wnt signaling pathway in urological cancer, Epigenetics 5, 343–351.PubMedCrossRefGoogle Scholar
  213. 213.
    Baylin, S. B., and Ohm, J. E. (2006) Epigenetic gene silencing in cancer—a mechanism for early oncogenic pathway addiction?, Nat Rev Cancer 6 107–116.PubMedCrossRefGoogle Scholar
  214. 214.
    Lind, G. E., Thorstensen, L., Lovig, T., Meling, G. I., Hamelin, R., Rognum, T. O., Esteller, M., and Lothe, R. A. (2004) A CpG island hypermethylation profile of primary colorectal carcinomas and colon cancer cell lines, Mol Cancer 3, 28.PubMedCrossRefGoogle Scholar
  215. 215.
    Bastian, P. J., Palapattu, G. S., Yegnasubra-manian, S., Lin, X., Rogers, C. G., Mangold, L. A., Trock, B., Eisenberger, M., Partin, A. W., and Nelson, W. G. (2007) Prognostic value of preoperative serum cell-free circulating DNA in men with prostate cancer undergoing radical prostatectomy, Clin Cancer Res 13, 5361–5367.PubMedCrossRefGoogle Scholar
  216. 216.
    Bastian, P. J., Yegnasubramanian, S., Palapattu, G. S., Rogers, C. G., Lin, X., De Marzo, A. M., and Nelson, W. G. (2004) Molecular biomarker in prostate cancer: the role of CpG island hypermethylation, Eur Urol 46 698708.PubMedCrossRefGoogle Scholar
  217. 217.
    Richiardi, L., Fiano, V., Vizzini, L., De Marco, L., Delsedime, L., Akre, O., Tos, A. G., and Merletti, F. (2009) Promoter methylation in APC, RUNX3, and GSTP1 and mortality in prostate cancer patients, J Clin Oncol 27, 3161–3168.PubMedCrossRefGoogle Scholar
  218. 218.
    Gao, X., Porter, A. T., and Honn, K. V. (1997) Involvement of the multiple tumor suppressor genes and 12-lipoxygenase in human prostate cancer. Therapeutic implications, Adv Exp Med Biol 407, 41–53.PubMedGoogle Scholar
  219. 219.
    Kito, H., Suzuki, H., Ichikawa, T., Sekita, N., Kamiya, N., Akakura, K., Igarashi, T., Nakayama, T., Watanabe, M., Harigaya, K., and Ito, H. (2001) Hypermethylation of the CD44 gene is associated with progression and metastasis of human prostate cancer, Prostate 49, 110–115.PubMedCrossRefGoogle Scholar
  220. 220.
    Lou, W., Krill, D., Dhir, R., Becich, M. J., Dong, J. T., Frierson, H. F., Jr., Isaacs, W. B., Isaacs, J. T., and Gao, A. C. (1999) Methylation of the CD44 metastasis suppressor gene in human prostate cancer, Cancer Res 59, 2329–2331.PubMedGoogle Scholar
  221. 221.
    Graziano, F., Humar, B., and Guilford, P. (2003) The role of the E-cadherin gene (CDH1) in diffuse gastric cancer susceptibility: from the laboratory to clinical practice, Ann Oncol 14, 1705–1713.PubMedCrossRefGoogle Scholar
  222. 222.
    Li, L. C., Zhao, H., Nakajima, K., Oh, B. R., Ribeiro Filho, L. A., Carroll, P., and Dahiya, R. (2001) Methylation of the E-cadherin gene promoter correlates with progression of prostate cancer, J Urol 166, 705–709.PubMedCrossRefGoogle Scholar
  223. 223.
    Saha, B., Kaur, P., Tsao-Wei, D., Naritoku, W. Y., Groshen, S., Datar, R. H., Jones, L. W., and Imam, S. A. (2008) Unmethylated E-cadherin gene expression is significantly associated with metastatic human prostate cancer cells in bone, Prostate 68, 1681–1688.PubMedCrossRefGoogle Scholar
  224. 224.
    Riou, P., Saffroy, R., Comoy, J., Gross-Goupil, M., Thiery, J. P., Emile, J. F., Azoulay, D., Piatier-Tonneau, D., Lemoine, A., and Debuire, B. (2002) Investigation in liver tissues and cell lines of the transcription of 13 genes mapping to the 16q24 region that are frequently deleted in hepatocellular carcinoma, Clin Cancer Res 8, 3178–3186.PubMedGoogle Scholar
  225. 225.
    Toyooka, K. O., Toyooka, S., Virmani, A. K., Sathyanarayana, U. G., Euhus, D. M., Gilcrease, M., Minna, J. D., and Gazdar, A. F. (2001) Loss of expression and aberrant methylation of the CDH13 (H-cadherin) gene in breast and lung carcinomas, Cancer Res 61, 4556–4560.PubMedGoogle Scholar
  226. 226.
    Alumkal, J. J., Zhang, Z., Humphreys, E. B., Bennett, C., Mangold, L. A., Carducci, M. A., Partin, A. W., Garrett-Mayer, E., DeMarzo, A. M., and Herman, J. G. (2008) Effect of DNA methylation on identification of aggressive prostate cancer, Urology 72, 1234–1239.PubMedCrossRefGoogle Scholar
  227. 227.
    Lee, S. W. (1996) H-cadherin, a novel cadherin with growth inhibitory functions and diminished expression in human breast cancer, Nat Med 2, 776–782.PubMedCrossRefGoogle Scholar
  228. 228.
    Mashimo, T., Watabe, M., Cuthbert, A. P., Newbold, R. F., Rinker-Schaeffer, C. W., Helfer, E., and Watabe, K. (1998) Human chromosome 16 suppresses metastasis but not tumorigenesis in rat prostatic tumor cells, Cancer Res 58, 4572–4576.PubMedGoogle Scholar
  229. 229.
    Salama, I., Malone, P. S., Mihaimeed, F., and Jones, J. L. (2008) A review of the S100 proteins in cancer, Eur J Surg Oncol 34, 357–364.PubMedCrossRefGoogle Scholar
  230. 230.
    Rehman, I., Cross, S. S., Catto, J. W., Leiblich, A., Mukherjee, A., Azzouzi, A. R., Leung, H. Y., and Hamdy, F. C. (2005) Promoter hyper-methylation of calcium binding proteins S100A6 and S100A2 in human prostate cancer, Prostate 65, 322–330.PubMedCrossRefGoogle Scholar
  231. 231.
    Gokaslan, Z. L., Chintala, S. K., York, J. E., Boyapati, V., Jasti, S., Sawaya, R., Fuller, G., Wildrick, D. M., Nicolson, G. L., and Rao, J. S. (1998) Expression and role of matrix metalloproteinases MMP-2 and MMP-9 in human spinal column tumors, Clin Exp Metastasis 16, 721–728.PubMedCrossRefGoogle Scholar
  232. 232.
    Gomez, D. E., Alonso, D. F., Yoshiji, H., and Thorgeirsson, U. P. (1997) Tissue inhibitors of metalloproteinases: structure, regulation and biological functions, Eur J Cell Biol 74, 111–122.PubMedGoogle Scholar
  233. 233.
    Imren, S., Kohn, D. B., Shimada, H., Blavier, L., and DeClerck, Y. A. (1996) Overexpression of tissue inhibitor of metalloproteinases-2 retroviral-mediated gene transfer in vivo inhibits tumor growth and invasion, Cancer Res 56, 2891–2895.PubMedGoogle Scholar
  234. 234.
    Mohanam, S., Wang, S. W., Rayford, A., Yamamoto, M., Sawaya, R., Nakajima, M., Liotta, L. A., Nicolson, G. L., Stetler-Stevenson, W. G., and Rao, J. S. (1995) Expression of tissue inhibitors of metalloproteinases: negative regulators of human glioblastoma invasion in vivo, Clin Exp Metastasis 13, 57–62.PubMedCrossRefGoogle Scholar
  235. 235.
    Pulukuri, S. M., Patibandla, S., Patel, J., Estes, N., and Rao, J. S. (2007) Epigenetic inactivation of the tissue inhibitor of metalloproteinase-2 (TIMP-2) gene in human prostate tumors, Oncogene 26, 5229–5237.PubMedCrossRefGoogle Scholar
  236. 236.
    Ross, J. S., Kaur, P., Sheehan, C. E., Fisher, H. A., Kaufman, R. A., Jr., and Kallakury, B. V. (2003) Prognostic significance of matrix metalloproteinase 2 and tissue inhibitor of metalloproteinase 2 expression in prostate cancer, Mod Pathol 16, 198–205.PubMedCrossRefGoogle Scholar
  237. 237.
    Han, X., Zhang, H., Jia, M., Han, G., and Jiang, W. (2004) Expression of TIMP-3 gene by construction of a eukaryotic cell expression vector and its role in reduction of metastasis in a human breast cancer cell line, Cell Mol Immunol 1, 308–310.PubMedGoogle Scholar
  238. 238.
    Deng, X., Bhagat, S., Dong, Z., Mullins, C., Chinni, S. R., and Cher, M. (2006) Tissue inhibitor of metalloproteinase-3 induces apoptosis in prostate cancer cells and confers increased sensitivity to paclitaxel, Eur J Cancer 42, 3267–3273.PubMedCrossRefGoogle Scholar
  239. 239.
    Finan, K. M., Hodge, G., Reynolds, A. M., Hodge, S., Holmes, M. D., Baker, A. H., and Reynolds, P. N. (2006) In vitro susceptibility to the pro-apoptotic effects of TIMP-3 gene delivery translates to greater in vivo efficacy versus gene delivery for TIMPs-1 or −2, Lung Cancer 53, 273–284.PubMedCrossRefGoogle Scholar
  240. 240.
    Smith, E., De Young, N. J., Tian, Z. Q., Caruso, M., Ruszkiewicz, A. R., Liu, J. F., Jamieson, G. G., and Drew, P. A. (2008) Methylation of TIMP3 in esophageal squamous cell carcinoma, World J Gastroenterol 14, 203–210.PubMedCrossRefGoogle Scholar
  241. 241.
    Fizazi, K. (2007) The role of Src in prostate cancer, Ann Oncol 18, 1765–1773.PubMedCrossRefGoogle Scholar
  242. 242.
    Posadas, E. M., Al-Ahmadie, H., Robinson, V. L., Jagadeeswaran, R., Otto, K., Kasza, K. E., Tretiakov, M., Siddiqui, J., Pienta, K. J., Stadler, W. M., Rinker-Schaeffer, C., and Salgia, R. (2009) FYN is overexpressed in human prostate cancer, BJU Int 103, 171–177.PubMedCrossRefGoogle Scholar
  243. 243.
    Sorensen, K. D., Borre, M., Orntoft, T. F., Dyrskjot, L., and Torring, N. (2008) Chromo-somal deletion, promoter hypermethylation and downregulation of FYN in prostate cancer, Int J Cancer 122, 509–519.PubMedCrossRefGoogle Scholar
  244. 244.
    Usmani, B. A., Shen, R., Janeczko, M., Papandreou, C. N., Lee, W. H., Nelson, W. G., Nelson, J. B., and Nanus, D. M. (2000) Methylation of the neutral endopeptidase gene promoter in human prostate cancers, Clin Cancer Res 6, 1664–1670.PubMedGoogle Scholar
  245. 245.
    Osman, I., Dai, J., Mikhail, M., Navarro, D., Taneja, S. S., Lee, P., Christos, P., Shen, R., and Nanus, D. M. (2006) Loss of neutral endopeptidase and activation of protein kinase B (Akt) is associated with prostate cancer progression, Cancer 107, 2628–2636.PubMedCrossRefGoogle Scholar
  246. 246.
    Osman, I., Yee, H., Taneja, S. S., Levinson, B., Zeleniuch-Jacquotte, A., Chang, C., Nobert, C., and Nanus, D. M. (2004) Neutral endopeptidase protein expression and prognosis in localized prostate cancer, Clin Cancer Res 10, 4096–4100.PubMedCrossRefGoogle Scholar
  247. 247.
    Friedberg, E. C. (2001) How nucleotide excision repair protects against cancer, Nat Rev Cancer 1, 22–33.PubMedCrossRefGoogle Scholar
  248. 248.
    Mullaart, E., Lohman, P. H., Berends, F., and Vijg, J. (1990) DNA damage metabolism and aging, Mutat Res 237, 189–210.PubMedCrossRefGoogle Scholar
  249. 249.
    Wood, R. D., Mitchell, M., Sgouros, J., and Lindahl, T. (2001) Human DNA repair genes, Science 291, 1284–1289.PubMedCrossRefGoogle Scholar
  250. 250.
    Wood, R. D., Mitchell, M., and Lindahl, T. (2005) Human DNA repair genes, 2005, Mutat Res 577, 275–283.PubMedCrossRefGoogle Scholar
  251. 251.
    Park, J. Y., Huang, Y., and Sellers, T. A. (2009) Single nucleotide polymorphisms in DNA repair genes and prostate cancer risk, Methods Mol Biol 471, 361–385.PubMedCrossRefGoogle Scholar
  252. 252.
    Kim, J. I., Suh, J. T., Choi, K. U., Kang, H. J., Shin, D. H., Lee, I. S., Moon, T. Y., and Kim, W. T. (2009) Inactivation of O6-methylguanine-DNA methyltrans­ferase in soft tissue sarcomas: association with K-ras mutations, Hum Pathol 40, 934–941.PubMedCrossRefGoogle Scholar
  253. 253.
    Mack, G. S. (2006) Epigenetic cancer therapy makes headway, J Natl Cancer Inst 98, 1443–1444.PubMedCrossRefGoogle Scholar
  254. 254.
    Muller, C. I., Ruter, B., Koeffler, H. P., and Lubbert, M. (2006) DNA hypermethylation of myeloid cells, a novel therapeutic target in MDS and AML, Curr Pharm Biotechnol 7, 315–321.PubMedCrossRefGoogle Scholar
  255. 255.
    Oki, Y., Aoki, E., and Issa, J. P. (2007) Decitabine-bedside to bench, Crit Rev Oncol Hematol 61, 140–152.PubMedCrossRefGoogle Scholar
  256. 256.
    Muller, A., and Florek, M. (2010) 5-Azacytidine/Azacitidine, Recent Results Cancer Res 184, 159–170.PubMedCrossRefGoogle Scholar
  257. 257.
    Woodson, K., Gillespie, J., Hanson, J., Emmert-Buck, M., Phillips, J. M., Linehan, W. M., and Tangrea, J. A. (2004) Heterogeneous gene methylation patterns among pre-invasive and cancerous lesions of the prostate: a histopathologic study of whole mount prostate specimens, Prostate 60, 25–31.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Division of Cancer Prevention and ControlsH. Lee Moffitt Cancer Center and Research InstituteTampaUSA

Personalised recommendations