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Role of PI3K–Akt and PTEN in the Growth and Progression of Prostate Cancer

  • Haojie Huang
  • Donald J. Tindall
Part of the Current Clinical Oncology book series (CCO)

Keywords

Prostate Cancer Prostate Cancer Cell Metastatic Prostate Cancer PTEN Protein Forkhead Transcription Factor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Roy-Burman, P., Tindall, D.J., Robins, D.M. et al. (2005) Androgens and prostate cancer: are the descriptors valid? Cancer Biol. Ther. 4, 4–5.PubMedGoogle Scholar
  2. 2.
    Zegarra-Moro, O.L., Schmidt, L.J., Huang, H. and Tindall, D.J. (2002) Disruption of androgen receptor function inhibits proliferation of androgen-refractory prostate cancer cells. Cancer Res. 62, 1008–13.PubMedGoogle Scholar
  3. 3.
    Chen, C.D., Welsbie, D.S., Tran, C. et al. (2004) Molecular determinants of resistance to antiandrogen therapy. Nat. Med. 10, 33–9.PubMedGoogle Scholar
  4. 4.
    Deocampo, N.D., Huang, H. and Tindall, D.J. (2003) The role of PTEN in the progression and survival of prostate cancer. Minerva Endocrinol. 28, 145–53.PubMedGoogle Scholar
  5. 5.
    Cantley, L.C. and Neel, B.G. (1999) New insights into tumor suppression: PTEN suppresses tumor formation by restraining the phosphoinositide 3-kinase/AKT pathway. Proc. Natl. Acad. Sci. USA 96, 4240–5.PubMedGoogle Scholar
  6. 6.
    Downward, J. (1998) Mechanisms and consequences of activation of protein kinase B/Akt. Curr. Opin. Cell Biol. 10, 262–7.PubMedGoogle Scholar
  7. 7.
    Toker, A. and Newton, A.C. (2000) Akt/protein kinase B is regulated by autophosphorylation at the hypothetical PDK-2 site. J. Biol. Chem. 275, 8271–4.PubMedGoogle Scholar
  8. 8.
    Persad, S., Attwell, S., Gray, V. et al. (2001) Regulation of protein kinase B/Akt-serine 473 phosphorylation by integrin-linked kinase: critical roles for kinase activity and amino acids arginine 211 and serine 343. J. Biol. Chem. 276, 27462–9.PubMedGoogle Scholar
  9. 9.
    Feng, J., Park, J., Cron, P., Hess, D. and Hemmings, B.A. (2004) Identification of a PKB/Akt hydrophobic motif Ser-473 kinase as DNA-dependent protein kinase. J. Biol. Chem. 279, 41189–96.PubMedGoogle Scholar
  10. 10.
    Sarbassov, D.D., Guertin, D.A., Ali, S.M. and Sabatini, D.M. (2005) Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science 307, 1098–101.PubMedGoogle Scholar
  11. 11.
    Brunet, A., Bonni, A., Zigmond, M.J. et al. (1999) Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell 96, 857–68.PubMedGoogle Scholar
  12. 12.
    Datta, S.R., Dudek, H., Tao, X. et al. (1997) Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell 91, 231–41.PubMedGoogle Scholar
  13. 13.
    Inoki, K., Li, Y., Zhu, T., Wu, J. and Guan, K.L. (2002) TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling. Nat. Cell Biol. 4, 648–57.PubMedGoogle Scholar
  14. 14.
    Cross, D.A., Alessi, D.R., Cohen, P., Andjelkovich, M. and Hemmings, B.A. (1995) Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B. Nature 378, 785–9.PubMedGoogle Scholar
  15. 15.
    Zhou, B.P., Liao, Y., Xia, W., Zou, Y., Spohn, B. and Hung, M.C. (2001) HER-2/neu induces p53 ubiquitination via Akt-mediated MDM2 phosphorylation. Nat. Cell Biol. 3, 973–82.PubMedGoogle Scholar
  16. 16.
    Zhou, B.P., Liao, Y., Xia, W., Spohn, B., Lee, M.H. and Hung, M.C. (2001) Cytoplasmic localization of p21Cip1/WAF1 by Akt-induced phosphorylation in HER-2/neu-overexpressing cells. Nat. Cell Biol. 3, 245–52.PubMedGoogle Scholar
  17. 17.
    Wen, Y., Hu, M.C., Makino, K. et al. (2000) HER-2/neu promotes androgen-independent survival and growth of prostate cancer cells through the Akt pathway. Cancer Res. 60, 6841–5.PubMedGoogle Scholar
  18. 18.
    Myers, M.P., Stolarov, J.P., Eng, C. et al. (1997) P-TEN, the tumor suppressor from human chromosome 10q23, is a dual-specificity phosphatase. Proc. Natl. Acad. Sci. USA 94, 9052–7.PubMedGoogle Scholar
  19. 19.
    Maehama, T. and Dixon, J.E. (1998) The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate. J. Biol Chem. 273, 13375–8.PubMedGoogle Scholar
  20. 20.
    Myers, M.P., Pass, I., Batty, I.H. et al. (1998) The lipid phosphatase activity of PTEN is critical for its tumor supressor function. Proc. Natl. Acad. Sci. USA 95, 13513–8.PubMedGoogle Scholar
  21. 21.
    Ramaswamy, S., Nakamura, N., Vazquez, F. et al. (1999) Regulation of G1 progression by the PTEN tumor suppressor protein is linked to inhibition of the phosphatidylinositol 3-kinase/Akt pathway. Proc. Natl. Acad. Sci. USA 96, 2110–5.PubMedGoogle Scholar
  22. 22.
    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, 1943–7.PubMedGoogle Scholar
  23. 23.
    Whang, Y.E., Wu, X., Suzuki, H. et al. (1998) Inactivation of the tumor suppressor PTEN/MMAC1 in advanced human prostate cancer through loss of expression. Proc. Natl. Acad. Sci. USA 95, 5246–50.PubMedGoogle Scholar
  24. 24.
    Wu, X., Senechal, K., Neshat, M.S., Whang, Y.E. and Sawyers, C.L. (1998) The PTEN/MMAC1 tumor suppressor phosphatase functions as a negative regulator of the phosphoinositide 3-kinase/Akt pathway. Proc. Natl. Acad. Sci. USA 95, 15587–91.PubMedGoogle Scholar
  25. 25.
    Huang, H., Cheville, J.C., Pan, Y., Roche, P.C., Schmidt, L.J. and Tindall, D.J. (2001) PTEN induces chemosensitivity in PTEN-mutated prostate cancer cells by suppression of Bcl-2 expression. J. Biol. Chem. 276, 38830–6.PubMedGoogle Scholar
  26. 26.
    Murillo, H., Huang, H., Schmidt, L.J., Smith, D.I. and Tindall, D.J. (2001) Role of PI3K signaling in survival and progression of LNCaP prostate cancer cells to the androgen refractory state. Endocrinology 142, 4795–805.PubMedGoogle Scholar
  27. 27.
    Seki, M., Iwakawa, J., Cheng, H. and Cheng, P.W. (2002) p53 and PTEN/MMAC1/TEP1 gene therapy of human prostate PC-3 carcinoma xenograft, using transferrin-facilitated lipofection gene delivery strategy. Hum. Gene. Ther. 13, 761–73.PubMedGoogle Scholar
  28. 28.
    Nakamura, N., Ramaswamy, S., Vazquez, F., Signoretti, S., Loda, M. and Sellers, W.R. (2000) Forkhead transcription factors are critical effectors of cell death and cell cycle arrest downstream of PTEN. Mol. Cell. Biol. 20, 8969–82.PubMedGoogle Scholar
  29. 29.
    Graff, J.R., Konicek, B.W., McNulty, A.M. et al. (2000) Increased AKT activity contributes to prostate cancer progression by dramatically accelerating prostate tumor growth and diminishing p27Kip1 expression. J. Biol. Chem. 275, 24500–5.PubMedGoogle Scholar
  30. 30.
    Mamillapalli, R., Gavrilova, N., Mihaylova, V.T. et al. (2001) PTEN regulates the ubiquitin-dependent degradation of the CDK inhibitor p27(KIP1) through the ubiquitin E3 ligase SCF(SKP2). Curr. Biol. 11, 263–7.PubMedGoogle Scholar
  31. 31.
    Lynch, R.L., Konicek, B.W., McNulty, A.M. et al. (2005) The progression of LNCaP human prostate cancer cells to androgen independence involves decreased FOXO3a expression and reduced p27KIP1 promoter transactivation. Mol. Cancer Res. 3, 163–9.PubMedGoogle Scholar
  32. 32.
    McDonnell, T.J., Troncoso, P., Brisbay, S.M. et al. (1992) Expression of the protooncogene bcl-2 in the prostate and its association with emergence of androgen-independent prostate cancer. Cancer Res. 52, 6940–4.PubMedGoogle Scholar
  33. 33.
    Gleave, M., Tolcher, A., Miyake, H. et al. (1999) Progression to androgen independence is delayed by adjuvant treatment with antisense Bcl-2 oligodeoxynucleotides after castration in the LNCaP prostate tumor model. Clin. Cancer Res. 5, 2891–8.PubMedGoogle Scholar
  34. 34.
    Huang, H., Zegarra-Moro, O.L., Benson, D. and Tindall, D.J. (2004) Androgens repress Bcl-2 expression via activation of the retinoblastoma (RB) protein in prostate cancer cells. Oncogene 23, 2161–76.PubMedGoogle Scholar
  35. 35.
    Grossmann, M.E., Huang, H. and Tindall, D.J. (2001) Androgen receptor signaling in androgen-refractory prostate cancer. J. Natl. Cancer Inst. 93, 1687–97.PubMedGoogle Scholar
  36. 36.
    Coffey, D.S. (1993) Prostate cancer. An overview of an increasing dilemma. Cancer 71, 880–6.PubMedGoogle Scholar
  37. 37.
    Pienta, K.J. and Esper, P.S. (1993) Risk factors for prostate cancer. Ann. Intern. Med. 118, 793–803.PubMedGoogle Scholar
  38. 38.
    Isaacs, J.T. (1984) Antagonistic effect of androgen on prostatic cell death. Prostate 5, 545–57.PubMedGoogle Scholar
  39. 39.
    Berchem, G.J., Bosseler, M., Sugars, L.Y., Voeller, H.J., Zeitlin, S. and Gelmann, E.P. (1995) Androgens induce resistance to bcl-2-mediated apoptosis in LNCaP prostate cancer cells. Cancer Res. 55, 735–8.PubMedGoogle Scholar
  40. 40.
    Kimura, K., Markowski, M., Bowen, C. and Gelmann, E.P. (2001) Androgen blocks apoptosis of hormone-dependent prostate cancer cells. Cancer Res. 61, 5611–8.PubMedGoogle Scholar
  41. 41.
    Carson, J.P., Kulik, G. and Weber, M.J. (1999) Antiapoptotic signaling in LNCaP prostate cancer cells: a survival signaling pathway independent of phosphatidylinositol 3’-kinase and Akt/protein kinase B. Cancer Res. 59, 1449–53.PubMedGoogle Scholar
  42. 42.
    Lin, J., Adam, R.M., Santiestevan, E. and Freeman, M.R. (1999) The phosphatidylinositol 3’-kinase pathway is a dominant growth factor-activated cell survival pathway in LNCaP human prostate carcinoma cells. Cancer Res. 59, 2891–7.PubMedGoogle Scholar
  43. 43.
    Huang, H., Muddiman, D.C. and Tindall, D.J. (2004) Androgens negatively regulate forkhead transcription factor FKHR (FOXO1) through a proteolytic mechanism in prostate cancer cells. J. Biol. Chem. 279, 13866–77.PubMedGoogle Scholar
  44. 44.
    Wang, S.I., Parsons, R. and Ittmann, M. (1998) Homozygous deletion of the PTEN tumor suppressor gene in a subset of prostate adenocarcinomas. Clin. Cancer Res. 4, 811–5.PubMedGoogle Scholar
  45. 45.
    Suzuki, H., Freije, D., Nusskern, D.R. et al. (1998) Interfocal heterogeneity of PTEN/MMAC1 gene alterations in multiple metastatic prostate cancer tissues. Cancer Res. 58, 204–9.PubMedGoogle Scholar
  46. 46.
    Cairns, P., Okami, K., Halachmi, S. et al. (1997) Frequent inactivation of PTEN/MMAC1 in primary prostate cancer. Cancer Res. 57, 4997–5000.PubMedGoogle Scholar
  47. 47.
    Feilotter, H.E., Nagai, M.A., Boag, A.H., Eng, C. and Mulligan, L.M. (1998) Analysis of PTEN and the 10q23 region in primary prostate carcinomas. Oncogene 16, 1743–8.PubMedGoogle Scholar
  48. 48.
    Vlietstra, R.J., van Alewijk, D.C., Hermans, K.G., van Steenbrugge, G.J. and Trapman, J. (1998) Frequent inactivation of PTEN in prostate cancer cell lines and xenografts. Cancer Res. 58, 2720–3.PubMedGoogle Scholar
  49. 49.
    Gray, I.C., Stewart, L.M., Phillips, S.M., et al. (1998) Mutation and expression analysis of the putative prostate tumour-suppressor gene PTEN. Br. J. Cancer 78, 1296–300.PubMedGoogle Scholar
  50. 50.
    Nemoto, S. and Finkel, T. 2002 Redox regulation of forkhead proteins through a p66shc-dependent signaling pathway. Science 295, 2450–2.PubMedGoogle Scholar
  51. 51.
    Lee, S.R., Yang, K.S., Kwon, J., Lee, C., Jeong, W. and Rhee, S.G. (2002) Reversible inactivation of the tumor suppressor PTEN by H2O2. J. Biol. Chem. 277, 20336–42.PubMedGoogle Scholar
  52. 52.
    Leslie, N.R. and Downes, C.P. (2002) PTEN: The down side of PI 3-kinase signalling. Cell. Signal. 14, 285–95.PubMedGoogle Scholar
  53. 53.
    Vazquez, F., Ramaswamy, S., Nakamura, N. and Sellers, W.R. (2000) Phosphorylation of the PTEN tail regulates protein stability and function. Mol. Cell. Biol. 20, 5010–8.PubMedGoogle Scholar
  54. 54.
    Torres, J. and Pulido, R. (2001) The tumor suppressor PTEN is phosphorylated by the protein kinase CK2 at its C terminus. Implications for PTEN stability to proteasome-mediated degradation. J. Biol. Chem. 276, 993–8.PubMedGoogle Scholar
  55. 55.
    Cheng, J.Q., Godwin, A.K., Bellacosa, A. et al. (1992) AKT2, a putative oncogene encoding a member of a subfamily of protein-serine/threonine kinases, is amplified in human ovarian carcinomas. Proc. Natl. Acad. Sci. USA 89, 9267–71.PubMedGoogle Scholar
  56. 56.
    Ruggeri, B.A., Huang, L., Wood, M., Cheng, J.Q. and Testa, J.R. (1998) Amplification and overexpression of the AKT2 oncogene in a subset of human pancreatic ductal adenocarcinomas. Mol. Carcinog. 21, 81–6.PubMedGoogle Scholar
  57. 57.
    Liao, Y., Grobholz, R., Abel, U. et al. (2003) Increase of AKT/PKB expression correlates with gleason pattern in human prostate cancer. Int. J. Cancer 107, 676–80.PubMedGoogle Scholar
  58. 58.
    Malik, S.N., Brattain, M., Ghosh, P.M. et al. (2002) Immunohistochemical demonstration of phospho-Akt in high Gleason grade prostate cancer. Clin. Cancer Res. 8, 1168–71.PubMedGoogle Scholar
  59. 59.
    Kreisberg, J.I., Malik, S.N., Prihoda, T.J. et al. (2004) Phosphorylation of Akt (Ser473) is an excellent predictor of poor clinical outcome in prostate cancer. Cancer Res. 64, 5232–6.PubMedGoogle Scholar
  60. 60.
    Mellon, K., Thompson, S., Charlton, R.G. et al. (1992) p53, c-erbB-2 and the epidermal growth factor receptor in the benign and malignant prostate. J. Urol. 147, 496–9.PubMedGoogle Scholar
  61. 61.
    Chan, J.M., Stampfer, M.J., Giovannucci, E. et al. (1998) Plasma insulin-like growth factor-I and prostate cancer risk: a prospective study. Science 279, 563–6.PubMedGoogle Scholar
  62. 62.
    Shayesteh, L., Lu, Y., Kuo, W.L. et al. (1999) PIK3CA is implicated as an oncogene in ovarian cancer. Nat. Genet. 21, 99–102.PubMedGoogle Scholar
  63. 63.
    Samuels, Y. and Velculescu, V.E. (2004) Oncogenic mutations of PIK3CA in human cancers. Cell Cycle 3, 1221–4.PubMedGoogle Scholar
  64. 64.
    Ogg, S., Paradis, S., Gottlieb, S. et al. (1997) The Fork head transcription factor DAF-16 transduces insulin-like metabolic and longevity signals in C. elegans. Nature 389, 994–9.PubMedGoogle Scholar
  65. 65.
    Lin, K., Dorman, J.B., Rodan, A. and Kenyon, C. (1997) daf-16: An HNF-3/forkhead family member that can function to double the life-span of Caenorhabditis elegans. Science 278, 1319–22.PubMedGoogle Scholar
  66. 66.
    Kops, G.J., de Ruiter, N.D., De Vries-Smits, A.M., Powell, D.R., Bos, J.L. and Burgering, B.M. (1999) Direct control of the Forkhead transcription factor AFX by protein kinase B. Nature 398, 630–4.PubMedGoogle Scholar
  67. 67.
    Tang, E.D., Nunez, G., Barr, F.G. and Guan, K.L. (1999) Negative regulation of the forkhead transcription factor FKHR by Akt. J. Biol. Chem. 274, 16741–6.PubMedGoogle Scholar
  68. 68.
    Biggs, W.H., 3rd, Meisenhelder, J., Hunter, T., Cavenee, W.K. and Arden, K.C. (1999) Protein kinase B/Akt-mediated phosphorylation promotes nuclear exclusion of the winged helix transcription factor FKHR1. Proc. Natl. Acad. Sci. USA 96, 7421–6.PubMedGoogle Scholar
  69. 69.
    Medema, R.H., Kops, G.J., Bos, J.L. and Burgering, B.M. (2000) AFX-like Forkhead transcription factors mediate cell-cycle regulation by Ras and PKB through p27kip1. Nature 404, 782–7.PubMedGoogle Scholar
  70. 70.
    Ramaswamy, S., Nakamura, N., Sansal, I., Bergeron, L. and Sellers, W.R. (2002) A novel mechanism of gene regulation and tumor suppression by the transcription factor FKHR. Cancer Cell 2, 81–91.PubMedGoogle Scholar
  71. 71.
    Schmidt, M., Fernandez de Mattos, S., van der Horst, A. et al. (2002) Cell cycle inhibition by FOXO forkhead transcription factors involves downregulation of cyclin D. Mol. Cell. Biol. 22, 7842–52.PubMedGoogle Scholar
  72. 72.
    Alvarez, B., Martinez, A.C., Burgering, B.M. and Carrera, A.C. (2001) Forkhead transcription factors contribute to execution of the mitotic programme in mammals. Nature 413, 744–7.PubMedGoogle Scholar
  73. 73.
    Tran, H., Brunet, A., Grenier, J.M. et al. (2002) DNA repair pathway stimulated by the forkhead transcription factor FOXO3a through the Gadd45 protein. Science 296, 530–4.PubMedGoogle Scholar
  74. 74.
    Furukawa-Hibi, Y., Yoshida-Araki, K., Ohta, T., Ikeda, K. and Motoyama, N. (2002) FOXO forkhead transcription factors induce G(2)-M checkpoint in response to oxidative stress. J. Biol. Chem. 277, 26729–32.PubMedGoogle Scholar
  75. 75.
    Gilley, J., Coffer, P.J. and Ham, J. (2003) FOXO transcription factors directly activate bim gene expression and promote apoptosis in sympathetic neurons. J. Cell Biol. 162, 613–22.PubMedGoogle Scholar
  76. 76.
    Modur, V., Nagarajan, R., Evers, B.M. and Milbrandt, J. (2002) FOXO proteins regulate tumor necrosis factor-related apoptosis inducing ligand expression. Implications for PTEN mutation in prostate cancer. J. Biol. Chem. 277, 47928–37.PubMedGoogle Scholar
  77. 77.
    Accili, D. and Arden, K.C. (2004) FOXOs at the crossroads of cellular metabolism, differentiation, and transformation. Cell 117, 421–6.PubMedGoogle Scholar
  78. 78.
    Hosaka, T., Biggs, W.H., 3rd, Tieu, D. et al. (2004) Disruption of forkhead transcription factor (FOXO) family members in mice reveals their functional diversification. Proc. Natl. Acad. Sci. USA 101, 2975–80.PubMedGoogle Scholar
  79. 79.
    Furuyama, T., Kitayama, K., Shimoda, Y. et al. (2004) Abnormal angiogenesis in FOXO1 (Fkhr)-deficient mice. J. Biol. Chem. 279, 34741–9.PubMedGoogle Scholar
  80. 80.
    Daly, C., Wong, V., Burova, E. et al. (2004) Angiopoietin-1 modulates endothelial cell function and gene expression via the transcription factor FKHR (FOXO1). Genes Dev. 18, 1060–71.PubMedGoogle Scholar
  81. 81.
    Castrillon, D.H., Miao, L., Kollipara, R., Horner, J.W. and DePinho, R.A. (2003) Suppression of ovarian follicle activation in mice by the transcription factor FOXO3a. Science 301, 215–8.PubMedGoogle Scholar
  82. 82.
    Nakae, J., Park, B.C. and Accili, D. (1999) Insulin stimulates phosphorylation of the forkhead transcription factor FKHR on serine 253 through a Wortmannin-sensitive pathway. J. Biol. Chem. 274, 15982–5.PubMedGoogle Scholar
  83. 83.
    Rena, G., Guo, S., Cichy, S.C., Unterman, T.G. and Cohen, P. (1999) Phosphorylation of the transcription factor forkhead family member FKHR by protein kinase B. J. Biol. Chem. 274, 17179–83.PubMedGoogle Scholar
  84. 84.
    Guo, S., Rena, G., Cichy, S., He, X., Cohen, P. and Unterman, T. (1999) Phosphorylation of serine 256 by protein kinase B disrupts transactivation by FKHR and mediates effects of insulin on insulin-like growth factor-binding protein-1 promoter activity through a conserved insulin response sequence. J. Biol. Chem. 274, 17184–92.PubMedGoogle Scholar
  85. 85.
    Brunet, A., Sweeney, L.B., Sturgill, J.F. et al. (2004) Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase. Science 303, 2011–5.PubMedGoogle Scholar
  86. 86.
    Sunayama, J., Tsuruta, F., Masuyama, N. and Gotoh, Y. (2005) JNK antagonizes Akt-mediated survival signals by phosphorylating 14–3-3. J. Cell Biol. 170, 295–304.PubMedGoogle Scholar
  87. 87.
    Hu, M.C., Lee, D.F., Xia, W. et al. (2004) IkappaB kinase promotes tumorigenesis through inhibition of forkhead FOXO3a. Cell 117, 225–37.PubMedGoogle Scholar
  88. 88.
    Plas, D.R. and Thompson, C.B. (2003) Akt activation promotes degradation of tuberin and FOXO3a via the proteasome. J. Biol. Chem. 278, 12361–6.PubMedGoogle Scholar
  89. 89.
    Matsuzaki, H., Daitoku, H., Hatta, M., Tanaka, K. and Fukamizu, A. (2003) Insulin-induced phosphorylation of FKHR (FOXO1) targets to proteasomal degradation. Proc. Natl. Acad. Sci. USA 100, 11285–90.PubMedGoogle Scholar
  90. 90.
    Aoki, M., Jiang, H. and Vogt, P.K. (2004) Proteasomal degradation of the FOXO1 transcriptional regulator in cells transformed by the P3k and Akt oncoproteins. Proc. Natl. Acad. Sci. USA 101, 13613–7.PubMedGoogle Scholar
  91. 91.
    Huang, H., Regan, K.M., Wang, F. et al. (2005) Skp2 inhibits FOXO1 in tumor suppression through ubiquitin-mediated degradation. Proc. Natl. Acad. Sci. USA 102, 1649–54.PubMedGoogle Scholar
  92. 92.
    Papandreou, C.N., Daliani, D.D., Nix, D. et al. (2004) Phase I trial of the proteasome inhibitor bortezomib in patients with advanced solid tumors with observations in androgen-independent prostate cancer. J. Clin. Oncol. 22, 2108–21.PubMedGoogle Scholar
  93. 93.
    Yang, G., Ayala, G., De Marzo, A. et al. (2002) Elevated Skp2 protein expression in human prostate cancer: association with loss of the cyclin-dependent kinase inhibitor p27 and PTEN and with reduced recurrence-free survival. Clin. Cancer Res. 8, 3419–26.PubMedGoogle Scholar
  94. 94.
    Ben-Izhak, O., Lahav-Baratz, S., Meretyk, S. et al. (2003) Inverse relationship between Skp2 ubiquitin ligase and the cyclin dependent kinase inhibitor p27Kip1 in prostate cancer. J. Urol. 170, 241–5.PubMedGoogle Scholar
  95. 95.
    Latres, E., Chiarle, R., Schulman, B.A. et al. (2001) Role of the F-box protein Skp2 in lymphomagenesis. Proc. Natl. Acad. Sci. USA 98, 2515–20.PubMedGoogle Scholar
  96. 96.
    Signoretti, S., Di Marcotullio, L., Richardson, A. et al. (2002) Oncogenic role of the ubiquitin ligase subunit Skp2 in human breast cancer. J. Clin. Invest. 110, 633–41.PubMedGoogle Scholar
  97. 97.
    Nasrin, N., Ogg, S., Cahill, C.M. et al. (2000) DAF-16 recruits the CREB-binding protein coactivator complex to the insulin-like growth factor binding protein 1 promoter in HepG2 cells. Proc. Natl. Acad. Sci. USA 97, 10412–7.PubMedGoogle Scholar
  98. 98.
    Fukuoka, M., Daitoku, H., Hatta, M., Matsuzaki, H., Umemura, S. and Fukamizu, A. (2003) Negative regulation of forkhead transcription factor AFX (FOXO4) by CBP-induced acetylation. Int. J. Mol. Med. 12, 503–8.PubMedGoogle Scholar
  99. 99.
    Tissenbaum, H.A. and Guarente, L. (2001) Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans. Nature 410, 227–30.PubMedGoogle Scholar
  100. 100.
    Motta, M.C., Divecha, N., Lemieux, M. et al. (2004) Mammalian SIRT1 represses forkhead transcription factors. Cell 116, 551–63.PubMedGoogle Scholar
  101. 101.
    van der Horst, A., Tertoolen, L.G., de Vries-Smits, L.M., Frye, R.A., Medema, R.H. and Burgering, B.M. (2004) FOXO4 is acetylated upon peroxide stress and deacetylated by the longevity protein hSir2(SIRT1). J. Biol. Chem. 279, 28873–9.PubMedGoogle Scholar
  102. 102.
    Daitoku, H., Hatta, M., Matsuzaki, H. et al. (2004) Silent information regulator 2 potentiates FOXO1-mediated transcription through its deacetylase activity. Proc. Natl. Acad. Sci. USA 101, 10042–7.PubMedGoogle Scholar
  103. 103.
    Matsuzaki, H., Daitoku, H., Hatta, M., Aoyama, H., Yoshimochi, K. and Fukamizu, A. (2005) Acetylation of FOXO1 alters its DNA-binding ability and sensitivity to phosphorylation. Proc. Natl. Acad. Sci. USA 102, 11278–83.PubMedGoogle Scholar
  104. 104.
    Debes, J.D., Sebo, T.J., Lohse, C.M., Murphy, L.M., Haugen de, A.L. and Tindall, D.J. (2003) p300 in prostate cancer proliferation and progression. Cancer Res. 63, 7638–40.PubMedGoogle Scholar
  105. 105.
    Linja, M.J., Porkka, K.P., Kang, Z. et al. (2004) Expression of androgen receptor coregulators in prostate cancer. Clin. Cancer Res. 10, 1032–40.PubMedGoogle Scholar
  106. 106.
    Comuzzi, B., Lambrinidis, L., Rogatsch, H. et al. (2003) The transcriptional co-activator cAMP response element-binding protein-binding protein is expressed in prostate cancer and enhances androgen- and anti-androgen-induced androgen receptor function. Am. J. Pathol. 162, 233–41.PubMedGoogle Scholar
  107. 107.
    Di Cristofano, A., Pesce, B., Cordon-Cardo, C. and Pandolfi, P.P. (1998) Pten is essential for embryonic development and tumour suppression. Nat. Genet. 19, 348–55.PubMedGoogle Scholar
  108. 108.
    Podsypanina, K., Ellenson, L.H., Nemes, A. et al. (1999) Mutation of Pten/Mmac1 in mice causes neoplasia in multiple organ systems. Proc. Natl. Acad. Sci. USA 96, 1563–8.PubMedGoogle Scholar
  109. 109.
    Di Cristofano, A., De Acetis, M., Koff, A., Cordon-Cardo, C. and Pandolfi, P.P. (2001) Pten and p27KIP1 cooperate in prostate cancer tumor suppression in the mouse. Nat. Genet. 27, 222–4.PubMedGoogle Scholar
  110. 110.
    Gao, H., Ouyang, X., Banach-Petrosky, W. et al. (2004) A critical role for p27kip1 gene dosage in a mouse model of prostate carcinogenesis. Proc. Natl. Acad. Sci. USA 101, 17204–9.PubMedGoogle Scholar
  111. 111.
    You, M.J., Castrillon, D.H., Bastian, B.C. et al. (2002) Genetic analysis of Pten and Ink4a/Arf interactions in the suppression of tumorigenesis in mice. Proc. Natl. Acad. Sci. USA 99, 1455–60.PubMedGoogle Scholar
  112. 112.
    Abate-Shen, C., Banach-Petrosky, W.A., Sun, X. et al. (2003) Nkx3.1; Pten mutant mice develop invasive prostate adenocarcinoma and lymph node metastases. Cancer Res. 63, 3886–90.PubMedGoogle Scholar
  113. 113.
    Ma, L., Teruya-Feldstein, J., Behrendt, N. et al. (2005) Genetic analysis of Pten and Tsc2 functional interactions in the mouse reveals asymmetrical haploinsufficiency in tumor suppression. Genes Dev. 19, 1779–86.PubMedGoogle Scholar
  114. 114.
    Lesche, R., Groszer, M., Gao, J. et al. (2002) Cre/loxP-mediated inactivation of the murine Pten tumor suppressor gene. Genesis 32, 148–9.PubMedGoogle Scholar
  115. 115.
    Wu, X., Wu, J., Huang, J. et al. (2001) Generation of a prostate epithelial cell-specific Cre transgenic mouse model for tissue-specific gene ablation. Mech. Dev. 101, 61–9.PubMedGoogle Scholar
  116. 116.
    Wang, S., Gao, J., Lei, Q. et al. (2003) Prostate-specific deletion of the murine Pten tumor suppressor gene leads to metastatic prostate cancer. Cancer Cell 4, 209–21.PubMedGoogle Scholar
  117. 117.
    Trotman, L.C., Niki, M., Dotan, Z.A. et al. (2003) Pten dose dictates cancer progression in the prostate. PLoS Biol. 1, E59.PubMedGoogle Scholar
  118. 118.
    Ma, X., Ziel-van der Made, A.C., Autar, B. et al. (2005) Targeted biallelic inactivation of Pten in the mouse prostate leads to prostate cancer accompanied by increased epithelial cell proliferation but not by reduced apoptosis. Cancer Res. 65, 5730–9.PubMedGoogle Scholar
  119. 119.
    Backman, S.A., Ghazarian, D., So, K. et al. (2004) Early onset of neoplasia in the prostate and skin of mice with tissue-specific deletion of Pten. Proc. Natl. Acad. Sci. USA 101, 1725–30.PubMedGoogle Scholar
  120. 120.
    Majumder, P.K., Febbo, P.G., Bikoff, R. et al. (2004) mTOR inhibition reverses Akt-dependent prostate intraepithelial neoplasia through regulation of apoptotic and HIF-1-dependent pathways. Nat. Med. 10, 594–601.PubMedGoogle Scholar
  121. 121.
    Yoeli-Lerner, M., Yiu, G.K., Rabinovitz, I., Erhardt, P., Jauliac, S. and Toker, A. (2005) Akt blocks breast cancer cell motility and invasion through the transcription factor NFAT. Mol. Cell. 20, 539–50.PubMedGoogle Scholar

Copyright information

© Humana Press 2008

Authors and Affiliations

  • Haojie Huang
  • Donald J. Tindall

There are no affiliations available

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