Skip to main content
SpringerLink
Log in

Tumor Suppressor Genes in Lung Cancer

  • Protocol
Tumor Suppressor Genes

Part of the book series: Methods in Molecular Biology™ ((MIMB,volume 222))

Abstract

Lung cancer is the number-one cancer killer of both men and women in the United States, killing more than 150,000 people every year. Lung cancer consists of two broad groups: small-cell lung cancers (SCLC), which account for about 25% of bronchogenic carcinomas, and the remaining tumors, non-small-cell lung cancers (NSCLC). SCLC cells possess neuroendrocrine-like properties, whereas most NSCLC lack these functions and can be divided into three major subtypes, adenocarcinoma, squamous cell carcinoma (SCC), and large cell carcinoma (LC). SCLC is one of the most virulent forms of human cancer, characterized by early dissemination and aggressive clinical evolution as compared to NSCLC. The initial responsiveness of SCLC to anticancer drugs and radiation treatment contrasts with the relative resistance of NSCLC to the same types of interventions. The reasons for the differences between SCLC and NSCLC are not fully understood, and one possible explanation may be resistance to killing via programmed cell death or apoptosis.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Wistuba, I. I. and Gazdar, A. F. (1999) Molecular abnormalities in the sequential development of lung carcinoma, in Molecular Pathology of Early Cancer, Srivastava, S., Henson, D. E., and Gazdar, A. F., eds.), IOS Press, Amsterdam, pp. 265–276.

    Google Scholar 

  2. Mao, L., Hruban, R. H., Boyle, J. O., Tockman, M., and Sidransky, D. (1994). Detection of oncogene mutations in sputum precedes diagnosis of lung cancer. Cancer Res. 54, 1634–1637.

    PubMed  CAS  Google Scholar 

  3. Wistuba, I. I., Barry, J., Behrens, C., et al. (2000) Molecular changes in the bronchial epithelium of patients with small cell lung cancer. Clin. Cancer Res. 6, 2604–2610.

    PubMed  CAS  Google Scholar 

  4. Sozzi, G., Sard, L., De Gregorio, L., et al. (1997) Association between cigarette smoking and FHIT gene alterations in lung cancer. Cancer Res. 57, 2121–2123.

    PubMed  CAS  Google Scholar 

  5. Franklin, W. A., Gazdar, A. F., Haney, J., et al. (1997) Widely dispersed p53 mutation in respiratory epithelium. J. Clin. Invest. 100, 2133–2137.

    Article  PubMed  CAS  Google Scholar 

  6. Orfanidou, D., Kalomenidis, J., Rasidakis, A., et al. (1998) Immunohistochemical detection of p53 protein in neoplastic, preneoplastic and normal bronchial mucosa specimens obtained during diagnostic bronchoscopy, Oncol. Rep. 5, 763–769.

    PubMed  CAS  Google Scholar 

  7. Keith, R. L., Miller, Y. E., Gemmill, R. M., et al. (2000) Angiogenic squamous dysplasia in bronchi of individuals at high risk for lung cancer. Clin. Cancer Res. 6, 1616–1625.

    PubMed  CAS  Google Scholar 

  8. Hirsch, F. R., Franklin, W. A., Gazdar, A. F., and Bunn, P. A., Jr. (2001) Early detection of lung cancer: clinical perspectives of recent advances in biology and radiology. Clin Cancer Res. 7, 5–22.

    PubMed  CAS  Google Scholar 

  9. Yashima, K., Litzky, L. A., Kaiser, L., et al. (1997) Telomerase expression in respiratory epithelium during the multistage pathogenesis of lung carcinomas. Cancer Res. 57, 2373–2377.

    PubMed  CAS  Google Scholar 

  10. Palmisano, W. A., Divine, K. K., Saccomanno, G., et al. (2000) Predicting lung cancer by detecting aberrant promoter methylation in sputum. Cancer Res. 60, 5954–5958.

    PubMed  CAS  Google Scholar 

  11. Ginsberg, R. J., Kris, M. G., and Armstrong, J. G. (1993) Cancer of the lung, in Cancer: Principles and Practice of Oncology, 3rd ed. DeVita, V. T. J. Hellman, S., and Rosenberg, S. A., eds.), Lippincott, Philadelphia, pp. 673–758.

    Google Scholar 

  12. Hanahan, D. and Weinberg, R. A. (2000) The hallmarks of cancer. Cell 100, 57–70.

    Article  PubMed  CAS  Google Scholar 

  13. Parkin, D. M., Pisani, P., Lopez, A. D., and Masuyer, E. (1994) At least one in seven cases of cancer is caused by smoking. Global estimates for 1985. Int. J. Cancer 59, 494–504.

    Article  PubMed  CAS  Google Scholar 

  14. Peto, R., Lopez, A. D., Boreham, J., Thun, M., Heath, C., Jr., and Doll, R. (1996) Mortality from smoking worldwide. Br. Med. Bull. 52, 12–21.

    Article  PubMed  CAS  Google Scholar 

  15. Peto, R., Darby, S., Deo, H., Silcocks, P., Whitley, E., and Doll, R. Smoking, smoking cessation, and lung cancer in the UK since 1950: combination of national statistics with two case-control studies [see comments]. Br. Med. J 321, 323–329.

    Google Scholar 

  16. Hecht, S. S. (1999) Tobacco smoke carcinogens and lung cancer. J. Natl. Cancer Inst. 91, 1194–1210.

    Article  PubMed  CAS  Google Scholar 

  17. Suzuki, H., Takahashi, T., Kuroishi, T., et al. (1992) p53 Mutations in non-small cell lung cancer in Japan: association between mutations and smoking. Cancer Res. 52, 734–736.

    PubMed  CAS  Google Scholar 

  18. Hernandez-Boussard, T. M. and Hainaut, P. (1998) A specific spectrum of p53 mutations in lung cancer from smokers: review of mutations compiled in the IARC p53 database. Environ Health Perspect. 106, 385–391.

    Article  PubMed  CAS  Google Scholar 

  19. Gealy, R., Zhang, L., Siegfried, J. M., Luketich, J. D., and Keohavong, P. (1999) Comparison of mutations in the p53 and K-ras genes in lung carcinomas from smoking and nonsmoking women. Cancer Epidemiol. Biomarkers Prev. 8, 297–302.

    PubMed  CAS  Google Scholar 

  20. Slebos, R. J., Hruban, R. H., Dalesio, O., Mooi, W. J., Offerhaus, G. J., and Rodenhuis, S. (1991) Relationship between K-ras oncogene activation and smoking in adenocarcinoma of the human lung. J. Natl. Cancer Inst. 83, 1024–1027.

    Article  PubMed  CAS  Google Scholar 

  21. Kim, D. H., Nelson, H. H., Wiencke, J. K., et al. (2001) p16(INK4a) and histology-specific methylation of CpG islands by exposure to tobacco smoke in non-small cell lung cancer. Cancer Res. 61, 3419–3424.

    PubMed  CAS  Google Scholar 

  22. Cloutier, J. F., Drouin, R., and Castonguay, A. (1999) Treatment of human cells with N-nitros(acetoxymethyl)methylamine: distribution patterns of piperidine-sensitive DNA damage at the nucleotide level of resolution are related to the sequence context. Chem. Res. To xicol. 12, 840–849.

    Article  CAS  Google Scholar 

  23. Pfeifer, G. P. (2000) p53 mutational spectra and the role of methylated CpG sequences. Mutat. Res. 450, 155–166.

    Article  PubMed  CAS  Google Scholar 

  24. Pfeifer, G. P., Tang, M., and Denissenko, M. F. (2000) Mutation hotspots and DNA methylation. Curr. Top. Microbiol. Immunol. 249, 1–19.

    Article  PubMed  CAS  Google Scholar 

  25. Kinzler, K. W. and Vogelstein, B. (1998) Landscaping the cancer terrain. Science 280, 1036–1037..

    Article  PubMed  CAS  Google Scholar 

  26. Virmani, A. K., Fong, K. M., Kodagoda, D., et al. (1998) Allelotyping demonstrates common and distinct patterns of chromosomal loss in human lung cancer types. Genes Chromosomes Cancer, 21, 308–319.

    Article  PubMed  CAS  Google Scholar 

  27. Girard, L., Zochbauer-Muller, S., Virmani, A. K., Gazdar, A. F., and Minna, J. D. (2000) Genome-wide allelotyping of lung cancer identifies new regions of allelic loss, differences between small cell lung cancer and non-small cell lung cancer, and loci clustering. Cancer Res. 60, 4894–4906.

    PubMed  CAS  Google Scholar 

  28. Wistuba, II, Montellano, F. D., Milchgrub, S., et al. (1997) Deletions Of Chromosome 3p are frequent and early events in the pathogenesis of uterine cervical carcinoma. Cancer Res. 57, 3154–3158.

    PubMed  CAS  Google Scholar 

  29. Wistuba, II, Behrens, C., Virmani, A. K., et al. (2000) High resolution chromosome 3p allelotyping of human lung cancer and preneoplastic/preinvasive bronchial epithelium reveals multiple, discontinuous sites of 3p allele loss and three regions of frequent breakpoints. Cancer Res. 60, 1949–1960.

    PubMed  CAS  Google Scholar 

  30. Lerman, M. I. and Minna, J. D. (2000) The 630-kb lung cancer homozygous deletion region on human chromosome 3p21.3: identification and evaluation of the resident candidate tumor suppressor genes. The International Lung Cancer Chromosome 3p21.3 Tumor Suppressor Gene Consortium. Cancer Res. 60, 6116–6133.

    PubMed  CAS  Google Scholar 

  31. 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.

    Article  PubMed  CAS  Google Scholar 

  32. Baylin, S. B., Esteller, M., Rountree, M. R., Bachman, K. E., Schuebel, K., and Herman, J. G. (2001) Aberrant patterns of DNA methylation, chromatin formation and gene expression in cancer. Hum. Mol. Genet. 10, 687–692.

    Article  PubMed  CAS  Google Scholar 

  33. Ng, H. H. and Bird, A. (2000) Histone deacetylases: silencers for hire. Trends Biochem. Sci. 25, 121–126.

    Article  PubMed  CAS  Google Scholar 

  34. Costello, J. F., Fruhwald, M. C., Smiraglia, D. J., Rush, et al. (2000) Aberrant CpG-island methylation has non-random and tumour-type-specific patterns. Nat. Genet. 24, 132–138.

    Article  PubMed  CAS  Google Scholar 

  35. Esteller, M., Sanchez-Cespedes, M., Rosell, R., Sidransky, D., Baylin, S. B., and Herman, J. G. (1999) Detection of aberrant promoter hypermethylation of tumor suppressor genes in serum DNA from non-small cell lung cancer patients. Cancer Res. 59, 67–70.

    PubMed  CAS  Google Scholar 

  36. Zochbauer-Muller, S., Fong, K. M., Virmani, A. K., Geradts, J., Gazdar, A. F., and Minna, J. D. (2001) Aberrant promoter methylation of multiple genes in non-small cell lung cancers. Cancer Res. 61, 249–255.

    PubMed  CAS  Google Scholar 

  37. Esteller, M., Corn, P. G., Baylin, S. B., and Herman, J. G. (2001) A gene hypermethylation profile of human cancer. Cancer Res. 61, 3225–3229.

    PubMed  CAS  Google Scholar 

  38. Lippman, S. M., Clayman, G. L., Huber, M. H., Benner, S. E., and Hong, W. K. (1995) Biology and reversal of aerodigestive tract carcinogenesis. Cancer Treat. Res. 74, 89–115.

    Article  PubMed  CAS  Google Scholar 

  39. Sun, S. Y., Wan, H., Yue, P., Hong, W. K., and Lotan, R. (2000) Evidence that retinoic acid receptor beta induction by retinoids is important for tumor cell growth inhibition. J. Biol. Chem. 275, 17149–17153.

    Article  PubMed  CAS  Google Scholar 

  40. Lotan, R. (1999) Aberrant expression of retinoid receptors and lung carcinogenesis [editorial]. J. Natl. Cancer Inst. 91, 989–991.

    Article  PubMed  CAS  Google Scholar 

  41. Xu, X. C., Lee, J. S., Lee, J. J., Morice, et al. (1999) Nuclear Retinoid Acid Receptor Beta in Bronchial Epithelium of Smokers Before and During Chemoprevention. J. Natl. Cancer Inst. 91, 1317–1321.

    Article  PubMed  CAS  Google Scholar 

  42. Virmani, A. K., Rathi, A., Zochbauer-Muller, S., et al. (2000) Promoter methylation and silencing of the retinoic acid receptor-beta gene in lung carcinomas. J. Natl. Cancer Inst. 92, 1303–1307.

    Article  PubMed  CAS  Google Scholar 

  43. Burbee, D. G., Forgacs, E., Zochbauer-Muller, S., et al. (2001) Epigenetic inactivation of RASSF1A in lung and breast cancers and malignant phenotype suppression. J. Natl. Cancer Inst. 93, 691–699.

    Article  PubMed  CAS  Google Scholar 

  44. Dammann, R., Li, C., Yoon, J. H., Chin, P. L., Bates, S., and Pfeifer, G. P. (2000) Epigenetic inactivation of a RAS association domain family protein from the lung tumour suppressor locus 3p21.3. Nat. Genet. 25, 315–319.

    Article  PubMed  CAS  Google Scholar 

  45. Ohta, M., Inoue, H., Cotticelli, M. G., et al. (1996) The FHIT gene, spanning the chromosome 3p14.2 fragile site and renal carcinoma-associated t(3;8) breakpoint, is abnormal in digestive tract cancers. Cell 84, 587–597.

    Article  PubMed  CAS  Google Scholar 

  46. Fong, K. M., Eric J. Biesterveld, Arvind K. Virmani, et al. (1997) FHIT and FRA3B 3p14.2 allele loss are common in lung cancer and preneoplastic bronchial lesions and are associated with cancer-related FHIT cDNA splicing abberrations. Cancer Res. 57, 2256–2267.

    PubMed  CAS  Google Scholar 

  47. Hayashi, S., Tanimoto, K., Hajiro-Nakanishi, K., et al. (1997) Abnormal FHIT transcripts in human breast carcinomas: a clinicopathological and epidemiological analysis of 61 Japanese cases. Cancer Res. 57, 1981–1985.

    PubMed  CAS  Google Scholar 

  48. Lin, P. M., Liu, T. C., Chang, J. G., Chen, T. P., and Lin, S. F. (1997) Aberrant FHIT transcripts in acute myeloid leukaemia. Br. J. Haematol. 99, 612–617.

    Article  PubMed  CAS  Google Scholar 

  49. Negrini, M., Monaco, C., Vorechovsky, I., et al. (1996) The FHIT gene at 3p14.2 is abnormal in breast carcinomas. Cancer Res. 56, 3173–3179.

    PubMed  CAS  Google Scholar 

  50. Yoshino, K., Enomoto, T., Nakamura, T., et al. (1998) Aberrant FHIT transcripts in squamous cell carcinoma of the uterine cervix. Int. J. Cancer 76, 176–181.

    Article  PubMed  CAS  Google Scholar 

  51. Zochbauer-Muller, S., Fong, K. M., Maitra, A., et al. (2001) 5′ CpG island methylation of the FHIT gene is correlated with loss of gene expression in lung and breast cancer. Cancer Res. 61, 3581–3585.

    PubMed  CAS  Google Scholar 

  52. Olopade, O. I., Buchhagen, D. L., Minna, J. D., et al. (1991) Deletions of the short arm of chromosome 9 that include the alpha and beta interferon genes are associated with lung cancers (meeting abstract). Proc. Annu. Meet. Am. Assoc. Cancer Res. 32, A1814.

    Google Scholar 

  53. Olopade, O. I., Buchhagen, D. L., Malik, K., et al. (1993) Homozygous loss of the interferon genes defines the critical region on 9p that is deleted in lung cancers. Cancer Res. 53, 2410–2415.

    PubMed  CAS  Google Scholar 

  54. Kamb, A., Gruis, N. A., Weaver-Feldhaus, J., et al. (1994) A cell cycle regulator potentially involved in genesis of many tumor types [see comments]. Science 264, 436–440.

    Article  PubMed  CAS  Google Scholar 

  55. Hayashi, N., Sugimoto, Y., Tsuchiya, E., Ogawa, M., and Nakamura, Y. (1994) Somatic mutations of the MTS (multiple tumor suppressor)1/CDK41 (cyclin-dependent kinase-4 inhibitor) gene in human primary non-small cell lung carcinomas. Biochem. Biophy. Res. Commun. 202, 1426–1430.

    Article  CAS  Google Scholar 

  56. Hannon, G. J. and Beach, D. (1994) p15INK4B is a potential effector of TGF-beta-induced cell cycle arrest. Nature 371, 257–261.

    Article  PubMed  CAS  Google Scholar 

  57. Washimi, O., Nagatake, M., Osada, H., et al. (1995) In vivo occurrence of p16 (MTS1) and p15 (MTS2) alterations preferentially in non-small cell lung cancers. Cancer Res. 55, 514–517.

    PubMed  CAS  Google Scholar 

  58. Xiao, S., Li, D., Corson, J. M., Vijg, J., and Fletcher, J. A. (1995) Codeletion of p15 and p16 genes in primary non-small cell lung carcinoma. Cancer Res. 55, 2968–2971.

    PubMed  CAS  Google Scholar 

  59. Hamada, K., Kohno, T., Takahashi, M., et al. (2000) Two regions of homozygous deletion clusters at chromosome band 9p21 in human lung cancer. Genes Chromosomes Cancer 27, 308–318.

    Article  PubMed  CAS  Google Scholar 

  60. Sato, S., Nakamura, Y., and Tsuchiya, E. Difference of allelotype between squamous cell carcinoma and adenocarcinoma of the lung. Cancer Res. 54, 5652–5655.

    Google Scholar 

  61. Kishimoto, Y., Sugio, K., Mitsudomi, T., et al. (1995) Frequent loss of the short arm of chromosome 9 in resected non-small-cell lung cancers from Japanese patients and its association with squamous cell carcinoma. J. Cancer Res. Clin. Oncol. 121, 291–296.

    Article  PubMed  CAS  Google Scholar 

  62. Otterson, G. A., Kratzke, R. A., Coxon, A., Kim, Y. W., and Kaye, F. J. (1994) Absence of p16INK4 protein is restricted to the subset of lung cancer lines that retains wildtype RB. Oncogene 9, 3375–3378.

    PubMed  CAS  Google Scholar 

  63. Harbour, J. W., Sali, S. L., Whang-Peng, J., Gazdar, A. F., Minna, J. D., and Kaye, F. J. (1988) Abnormalities in structure and expression of the human retinoblastoma gene in SCLC. Science 241, 353–357.

    Article  PubMed  CAS  Google Scholar 

  64. Shimizu, E., Coxon, A., Otterson, G. A., et al. (1994) RB protein status and clinical correlation from 172 cell lines representing lung cancer, extrapulmonary small cell carcinoma and mesothelioma. Oncogene 9, 2441–2448.

    PubMed  CAS  Google Scholar 

  65. Otterson, G. A., Kratzke, R. A., Coxon, A., Kim, Y. W., and Kaye, F. J. (1994) Absence of p16INK4 protein is restricted to the subset of lung cancer lines that retains wildtype RB. Oncogene 9, 3375–3378.

    PubMed  CAS  Google Scholar 

  66. Steck, P. A., Pershouse, M. A., Jasser, S. A., et al. (1997) Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers. Nat. Genet. 15, 356–362.

    Article  PubMed  CAS  Google Scholar 

  67. Li, J., Yen, C., Liaw, D., et al. (1997) Pten, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science 275, 1943–1947.

    Article  PubMed  CAS  Google Scholar 

  68. Li, D. M. and Sun, H. (1997) Tep1, encoded by a candidate tumor suppressor locus, is a novel protein tyrosine phosphatase regulated by transforming growth factor beta. Cancer Res. 57, 2124–2129.

    PubMed  CAS  Google Scholar 

  69. Ried, T., Petersen, I., Holtgreve-Grez, H., et al. (1994) Mapping of multiple DNA gains and losses in primary small cell lung carcinomas by comparative genomic hybridization. Cancer Res. 54, 1801–1806.

    PubMed  CAS  Google Scholar 

  70. Guldberg, P., Straten, P. T., Birck, A., Ahrenkiel, V., Kirkin, A. F., and Zeuthen, J. (1997) Disruption of the Mmac1/Pten gene by deletion or mutation is a frequent event in malignant melanoma. Cancer Res. 57, 3660–3663.

    PubMed  CAS  Google Scholar 

  71. Rhei, E., Kang, L., Bogomolniy, F., Federici, M. G., Borgen, P. I., and Boyd, J. (1997) Mutation analysis of the putative tumor suppressor gene Pten/Mmac1 in primary breast carcinomas. Cancer Res. 57, 3657–3659.

    PubMed  CAS  Google Scholar 

  72. Tashiro, H., Blazes, M. S., Wu, R., et al. (1997) Mutations in Pten are frequent in enometrial carcinoma but rare in other common gynecological malignancies. Cancer Res. 57, 3935–3940.

    PubMed  CAS  Google Scholar 

  73. Arch, E. M., Goodman, B. K., Vanwesep, R. A., et al. (1997) Deletion of PTENin a patient with Bannayan-Riley-Ruvalcaba-Syndrome suggests allelism with Cowden-Disease. Am. J. Med. Genet. 71, 489–493.

    Article  PubMed  CAS  Google Scholar 

  74. Liaw, D., Marsh, D. J., Li, J., et al. (1997) Germline mutations of the Pten gene in Cowden-Disease, an inherited breast and thyroid cancer syndrome. Nat. Genet. 16, 64–67.

    Article  PubMed  CAS  Google Scholar 

  75. Marsh, D. J., Dahia, P. L. M., Zheng, Z. M., et al. (1997) Germline mutations in Pten are present in Bannayan-Zonana Syndrome. Nat. Genet. 16, 333–334.

    Article  PubMed  CAS  Google Scholar 

  76. Tamura, M., Gu, J. G., Matsumoto, K., Aota, S., Parsons, R., and Yamada, K. M. (1998) Inhibition of cell migration, spreading, and focal adhesions by tumor suppressor PTEN. Science 280, 1614–1617.

    Article  PubMed  CAS  Google Scholar 

  77. Levin, N. A., Brzoska, P., Gupta, N., Minna, J. D., Gray, J. W., and Christman, M. F. (1994) Identification of frequent novel genetic alterations in small cell lung carcinoma. Cancer Res. 54, 5086–5091.

    PubMed  CAS  Google Scholar 

  78. Petersen, I., Langreck, H., Wolf, G., et al. (1997) Small-cell lung cancer is characterized by a high incidence of deletions on chromosomes 3p, 4q, 5q, 10q, 13q and 17p. Br. J. Cancer 75, 79–86.

    Article  PubMed  CAS  Google Scholar 

  79. Schwendel, A., Langreck, H., Reichel, M., et al. (1997) Primary small-cell lung carcinomas and their metastases are characterized by a recurrent pattern of genetic alterations. Int. J. Cancer 74, 86–93.

    Article  PubMed  CAS  Google Scholar 

  80. Forgacs, E., Biesterveld, E. J., Sekido, Y., et al. (1998) Mutation analysis of the PTEN/MMAC1 gene in lung cancer. Oncogene 17, 1557–1565.

    Article  PubMed  CAS  Google Scholar 

  81. Li, L. M. and Cohen, S. N. (1996) Tsg101—a novel tumor susceptibility gene isolated by controlled homozygous functional knockout of allelic loci in mammalian cells. Cell 85, 319–329.

    Article  PubMed  CAS  Google Scholar 

  82. Marklund, U., Brattsand, G., Shingler, V., and Gullberg, M. (1993) Serine 25 of oncoprotein 18 is a major cytosolic target for the mitogen-activated protein kinase. J. Biol. Chem. 268, 15039–15047.

    PubMed  CAS  Google Scholar 

  83. Roos, G., Brattsand, G., Landberg, G., Marklund, U., and Gullberg, M. (1993) Expression of oncoprotein 18 in human leukemias and lymphomas. Leukemia 7, 1538–1546.

    PubMed  CAS  Google Scholar 

  84. Hailat, N., Strahler, J., Melhem, R., et al. (1990) N-myc gene amplification in neuroblastoma is associated with altered phosphorylation of a proliferation related polypeptide (Op18). Oncogene 5, 1615–1618.

    PubMed  CAS  Google Scholar 

  85. Koonin, E. V. and Abagyan, R. A. (1997) TSG101 may be the prototype of a class of dominant negative ubiquitin regulators [letter]. Nat. Genet. 16, 330–331.

    Article  PubMed  CAS  Google Scholar 

  86. Ponting, C. P., Cai, Y. D., and Bork, P. (1997) The breast cancer gene product Tsg101—a regulator of ubiquitination. J. Mol. Med. 75, 467–469.

    Article  PubMed  CAS  Google Scholar 

  87. Li, L., Liao, J., Ruland, J., Mak, T. W., and Cohen, S. N. A (2001) TSG101/MDM2 regulatory loop modulates MDM2 degradation and MDM2/p53 feedback control. Proc. Natl. Acad. Sci. USA 98, 1619–1624.

    Article  PubMed  CAS  Google Scholar 

  88. Oh, Y., Proctor, M. L., Fan, Y. H., et al. (1998) TSG101 is not mutated in lung cancer but shortened transcript is frequently expressed in small cell lung cancer. Oncogene 16.

    Google Scholar 

  89. Wang, N. M., Chang, J. G., Liu, T. C., et al. (2000) Aberrant transcripts of FHIT, TSG101 and PTEN/MMAC1 genes in normal peripheral mononuclear cells. Int. J. Oncol. 16, 75–80.

    PubMed  CAS  Google Scholar 

  90. Takeichi, M. Cadherins in cancer: implications for invasion and metastasis, Curr Opin Cell Biol. 5: 806–11., 1993.

    Article  PubMed  CAS  Google Scholar 

  91. Takeichi, M., Watabe, M., Shibamoto, S., and Ito, F. (1994) Cadherin-dependent organization and disorganization of epithelial architecture. Princess Takamatsu Symp. 24, 28–37.

    PubMed  CAS  Google Scholar 

  92. Takeichi, M. (1995) Morphogenetic roles of classic cadherins. Curr. Opin. Cell Biol. 7, 619–627.

    Article  PubMed  CAS  Google Scholar 

  93. Behrens, J. (1993) The role of cell adhesion molecules in cancer invasion and metastasis. Breast Cancer Res. Treat. 24, 175–184.

    Article  PubMed  CAS  Google Scholar 

  94. 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.

    Article  PubMed  CAS  Google Scholar 

  95. Kase, S., Sugio, K., Yamazaki, K., Okamoto, T., Yano, T., and Sugimachi, K. (2000) Expression of E-cadherin and beta-catenin in human non-small cell lung cancer and the clinical significance. Clin. Cancer Res. 6, 4789–4796.

    PubMed  CAS  Google Scholar 

  96. Clavel, C. E., Nollet, F., Berx, G., et al. (2001) Expression of the E-cadherin-catenin complex in lung neuroendocrine tumours. J. Pathol. 194, 20–6.

    Article  PubMed  CAS  Google Scholar 

  97. Ranscht, B. and Dours-Zimmermann, M. T. (1991) T-cadherin, a novel cadherin cell adhesion molecule in the nervous system lacks the conserved cytoplasmic region. Neuron 7, 391–402.

    Article  PubMed  CAS  Google Scholar 

  98. Tsuda, H., Callen, D. F., Fukutomi, T., Nakamura, Y., and Hirohashi, S. (1994) Allele loss on chromosome 16q24.2-qter occurs frequently in breast cancers irrespectively of differences in phenotype and extent of spread. Cancer Res. 54, 513–517.

    PubMed  CAS  Google Scholar 

  99. Tsuda, H., Zhang, W. D., Shimosato, Y., et al. (1990) Allele loss on chromosome 16 associated with progression of human hepatocellular carcinoma. Proc. Natl. Acad. Sci. USA 87, 6791–6794.

    Article  PubMed  CAS  Google Scholar 

  100. Sato, M., Mori, Y., Sakurada, A., et al. (1998) Identification of a 910-kb region of common allelic loss in chromosome bands 16q24.1–q24.2 in human lung cancer. Genes Chromosomes Cancer 22, 1–8.

    Article  PubMed  CAS  Google Scholar 

  101. Carter, B. S., Ewing, C. M., Ward, W. S., et al. (1990) Allelic loss of chromosomes 16q and 10q in human prostate cancer. Proc. Natl. Acad. Sci. USA 87, 8751–8755.

    Article  PubMed  CAS  Google Scholar 

  102. Sato, M., Mori, Y., Sakurada, A., Fujimura, S., and Horii, A. (1998) The H-cadherin (CDH13) gene is inactivated in human lung cancer. Hum. Genet. 103, 96–101.

    Article  PubMed  CAS  Google Scholar 

  103. Toyooka, K. O., Toyooka, S., Virmani, A. K., et al. (2001) Loss of expression and aberrant methylation of the CDH13 (H-cadherin) gene in breast and lung carcinomas. Cancer Res. 61, 4556–4560.

    PubMed  CAS  Google Scholar 

  104. Zhong, Y., Delgado, Y., Gomez, J., Lee, S. W., and Perez-Soler, R. (2001) Loss of H-cadherin protein expression in human non-small cell lung cancer is associated with tumorigenicity. Clin. Cancer Res. 7, 1683–1687.

    PubMed  CAS  Google Scholar 

  105. Lee, S. W., Reimer, C. L., Campbell, D. B., Cheresh, P., Duda, R. B., and Kocher, O. (1998) H-cadherin expression inhibits in vitro invasiveness and tumor formation in vivo. Carcinogenesis 19, 1157–1159.

    Article  PubMed  CAS  Google Scholar 

  106. Takeuchi, T., Misaki, A., Fujita, J., Sonobe, H., and Ohtsuki, Y. (2001) T-cadherin (CDH13, H-cadherin) expression downregulated surfactant protein D in bronchioloalveolar cells. Virchows Arch. [bd438, 370–375.

    Article  PubMed  CAS  Google Scholar 

  107. Harris, C. C. (1996) p53: At the crossroads of molecular carcinogenesis and molecular epidemiology. J. Investig. Dermatol. Symp. Proc. 1, 115–118.

    PubMed  CAS  Google Scholar 

  108. Mitsudomi, T., Hamajima, N., Ogawa, M., and Takahashi, T. (2000) Prognostic significance of p53 alterations in patients with non-small cell lung cancer: a meta-analysis. Clin. Cancer Res. 6, 4055–4063.

    PubMed  CAS  Google Scholar 

  109. Huncharek, M., Kupelnick, B., Geschwind, J. F., and Caubet, J. F. (2000) Prognostic significance of p53 mutations in non-small cell lung cancer: a meta-analysis of 829 cases from eight published studies. Cancer Lett. 153, 219–226.

    Article  PubMed  CAS  Google Scholar 

  110. Fujiwara, T., Cai, D. W., Georges, R. N., Mukhopadhyay, T., Grimm, E. A., and Roth, J. A. (1994) Therapeutic effect of a retroviral wild-type p53 expression vector in an orthotopic lung cancer model [see comments]. J. Natl. Cancer Inst. 86, 1458–1462.

    Article  PubMed  CAS  Google Scholar 

  111. Minna, J. D. and Gazdar, A. F. (1996) Translational research comes of age [comment]. Nat. Med. 2, 974–975.

    Article  PubMed  CAS  Google Scholar 

  112. Hovens, C. M. and Kaye, A. H. (2001) The tumour suppressor protein NF2/merlin: the puzzle continues. J. Clin. Neurosci. 8, 4–7.

    Article  PubMed  CAS  Google Scholar 

  113. Sekido, Y., Pass, H. I., Bader, S., et al. (1995) Neurofibromatosis type 2 (NF2) gene is somatically mutated in mesothelioma but not in lung cancer. Cancer Res. 55, 1227–1231.

    PubMed  CAS  Google Scholar 

  114. Mulshine, J. L., Scott, F., Zhou, J., Avis, I., Vos, M., and Treston, A. M. (1997) Recent molecular advances in the approach to early lung cancer detection and intervention. Environ. Health Perspect. 105 Suppl 4, 935–939.

    Article  PubMed  CAS  Google Scholar 

  115. Ronai, Z. and Yakubovskaya, M. (1995) PCR in clinical diagnosis. J. Clin. Lab. Anal. 9, 269–283.

    Article  PubMed  CAS  Google Scholar 

  116. Ronai, Z., Yabubovskaya, M. S., Zhang, E., and Belitsky, G. A. (1996) K-ras mutation in sputum of patients with or without lung cancer. J. Cell Biochem. Suppl. 25, 172–176.

    Article  PubMed  CAS  Google Scholar 

  117. Yakubovskaya, M. S., Spiegelman, V., Luo, F. C., et al. (1995) High frequency of K-ras mutations in normal appearing lung tissues and sputum of patients with lung cancer. Int. J. Cancer 63, 810–814.

    Article  PubMed  CAS  Google Scholar 

  118. Mao, L., Lee, D. J., Tockman, M. S., Erozan, Y. S., Askin, F., and Sidransky, D. (1994) Microsatellite alterations as clonal markers for the detection of human cancer. Proc. Natl. Acad. Sci. USA 91, 9871–9875.

    Article  PubMed  CAS  Google Scholar 

  119. Miozzo, M., Sozzi, G., Musso, K., et al. (1996) Microsatellite alterations in bronchial and sputum specimens of lung cancer patients. Cancer Res. 56, 2285–2288.

    PubMed  CAS  Google Scholar 

  120. Sidransky, D., Von Eschenbach, A., Tsai, Y. C., et al. (1991) Identification of p53 gene mutations in bladder cancers and urine samples. Science 252, 706–709.

    Article  PubMed  CAS  Google Scholar 

  121. Yamashita, K., Kuba, T., Shinoda, H., Takahashi, E., and Okayasu, I. (1998) Detection of K-Ras point mutations in the supernatants of peritoneal and pleural effusions for diagnosis complementary to cytologic examination. Am. J. Clin. Pathol. 109, 704–711.

    PubMed  CAS  Google Scholar 

  122. Shibata, K., Mori, M., Kitano, S., and Akiyoshi, T. (1998) Detection of Ras gene mutations in peripheral blood of carcinoma patients using Cd45 immunomagnetic separation and nested mutant allele specific amplification. Int. J. Oncol. 12, 1333–1338.

    PubMed  CAS  Google Scholar 

  123. Sorenson, G. D., Pribish, D. M., Valone, F. H., Memoli, V. A., Bzik, D. J., and Yao, S. L. (1994) Soluble normal and mutated DNA sequences from single-copy genes in human blood. Cancer Epidemiol. Biomarkers Prev. 3, 67–71.

    PubMed  CAS  Google Scholar 

  124. Chen, X. Q., Stroun, M., Magnenat, J.-L., et al. (1996) Microsatellite alterations in plasma DNA of small cell lung cancer patients. Nat. Med. 2, 1033–1035.

    Article  PubMed  CAS  Google Scholar 

  125. Wistuba, II, Lam, S., Behrens, C., et al. (1997) Molecular damage in the bronchial epithelium of current and former smokers J. Natl. Cancer Inst. 89, 1366–1373.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Hamon Cancer Center UT Southwestern Medical Center, Dallas, TX

    Arvind K. Virmani & Adi F. Gazdar

Authors
  1. Arvind K. Virmani
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Adi F. Gazdar
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Departments of Medicine, Genetics, and Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA

    Wafik S. El-Deiry MD, PhD

Rights and permissions

Reprints and permissions

Copyright information

© 2003 Humana Press Inc.

About this protocol

Cite this protocol

Virmani, A.K., Gazdar, A.F. (2003). Tumor Suppressor Genes in Lung Cancer. In: El-Deiry, W.S. (eds) Tumor Suppressor Genes. Methods in Molecular Biology™, vol 222. Humana Press, Totowa, NJ. https://doi.org/10.1385/1-59259-328-3:097

Download citation

  • DOI: https://doi.org/10.1385/1-59259-328-3:097

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-0-89603-986-5

  • Online ISBN: 978-1-59259-328-6

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation