Advertisement

Cancer and Metastasis Reviews

, Volume 20, Issue 3–4, pp 207–223 | Cite as

Contribution of the Androgen Receptor to Prostate Cancer Predisposition and Progression

  • Grant Buchanan
  • Ryan A. Irvine
  • Gerhard A. Coetzee
  • Wayne D. Tilley
Article

Abstract

Although prostate cancer is heterogeneous in its etiology and progression, androgen signaling through the androgen receptor (AR) appears to be involved in all aspects of the disease, from initiation to development of treatment resistance. Lifetime exposure to a constitutively more active AR, encoded by AR alleles as defined by two translated polymorphic microsatellites (CAG and GGC), results in a significant increase in prostate cancer risk. The AR gene is amplified or a target for somatic gain-of-function mutations in metastatic prostate cancer. Gain-of-function AR gene mutations may result in inappropriate activation of the AR, thereby contributing to the failure of conventional androgen-ablation treatments. In cases where no genetically altered receptors are observed, altered signaling through the AR, achieved by cross-talk with other signaling pathways (e.g. kinase-mediated pathways) and/or inappropriate expression of coregulatory proteins, may contribute to disease progression. Thus, the AR-signaling axis contributes to many aspects of prostate cancer, including initiation, progression and resistance to current forms of therapy. This recognition represents a paradigm shift in our understanding of the molecular mechanisms involved in progression of prostate cancer, and provides insight into novel AR-targeted therapies which ultimately may be more effective than current forms of androgen ablation.

androgen-signaling axis CAG GGC mutation androgen-ablation therapy 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Roy AK, Lavrovsky Y, Song CS, Chen S, Jung MH, Velu NK, Bi BY, Chatterjee B: Regulation of androgen action. Vitam Horm 55: 309–352, 1999Google Scholar
  2. 2.
    Kokontis JM, Liao S: Molecular action of androgen in the normal and neoplastic prostate. Vitam Horm 55: 219–307, 1999Google Scholar
  3. 3.
    Tilley WD, Marcelli M, Wilson JD, McPhaul MJ: Characterization and expression of a cDNA encoding the human androgen receptor. Proc Natl Acad Sci USA 86: 327–331, 1989Google Scholar
  4. 4.
    O'Malley B: The steroid receptor superfamily: More excitement predicted for the future. Mol Endocrinol 4: 363–369, 1990Google Scholar
  5. 5.
    Stewart RJ, Panigrahy D, Flynn E, Folkman J: Vascular endothelial growth factor expression and tumor angiogenesis are regulated by androgens in hormone responsive human prostate carcinoma: Evidence for androgen dependent destabilization of vascular endothelial growth factor transcripts. J Urol 165: 688–693, 2001Google Scholar
  6. 6.
    Santen RJ: Clinical review 37: Endocrine treatment of prostate cancer. J Clin Endocrinol Metab 75: 685–689, 1992Google Scholar
  7. 7.
    Thenot S, Charpin M, Bonnet S, Cavailles V: Estrogen receptor cofactors expression in breast and endometrial human cancer cells. Mol Cell Endocrinol 156: 85–93, 1999Google Scholar
  8. 8.
    Kozlowski JM, Ellis WJ, Grayhack JT: Advanced prostatic carcinoma: Early v's late endocrine therapy. In: Andriole GL, Catalona WJ (eds) The Urologic Clinics of North America. WB Saunders Company, Philadelphia, 1991, pp 15–24Google Scholar
  9. 9.
    Linja MJ, Savinainen KJ, Saramaki OR, Tammela TL, Vessella RL, Visakorpi T: Amplification and overexpression of androgen receptor gene in hormone-refractory prostate cancer. Cancer Res 61: 3550–3555, 2001Google Scholar
  10. 10.
    Buchanan G, Yang M, Nahm SJ, Han G, Moore N, Bentel JM, Matusik RJ, Horsfall DJ, Marshall VR, Greenberg NM, Tilley WD: Mutations at the boundary of the hinge and ligand binding doma in of the androgen receptor confer increased transactivation function. Mol Endocrinol 15: 46–56, 2000Google Scholar
  11. 11.
    Yeh S, Lin HK, Kang HY, Thin TH, Lin MF, Chang C: From HER2/Neu signal cascade to androgen receptor and its coactivators: A novel pathway by induction of androgen target genes through MAP kinase in prostate cancer cells. Proc Natl Acad Sci USA 96: 5458–5463, 1999Google Scholar
  12. 12.
    Bentel JM, Tilley WD: Androgen receptors in prostate cancer. J Endocrinol 151: 1–11, 1996Google Scholar
  13. 13.
    Sadar MD, Hussain M, Bruchovsky N: Prostate cancer: Molecular biology of early progression to androgen independence. Endocr Relat Cancer 6: 487–502, 1999Google Scholar
  14. 14.
    Jenster G: The role of the androgen receptor in the development and progression of prostate cancer. Semin Oncol 26: 407–421, 1999Google Scholar
  15. 15.
    Kallio PJ, Pakvimo JJ, Janne OA: Genetic regulation of androgen action. Prostate (Suppl 6): 45–51, 1996Google Scholar
  16. 16.
    Edwards A, Hammond HA, Jin L, Caskey CT, Chakraborty R: Genetic variation at five trimeric and tetrameric tandem repeat loci in four human population groups. Genomics 12: 241–253, 1992Google Scholar
  17. 17.
    Giovannucci E, Stampfer MJ, Krithivas K, Brown M, Dahl D, Brufsky A, Talcott J, Hennekens CH, Kantoff PW: The CAG repeat within the androgen receptor gene and its relationship to prostate cancer. Proc Natl Acad Sci USA 94: 3320–3323, 1997Google Scholar
  18. 18.
    Rubinsztein DC, Leggo J, Coetzee GA, Irvine RA, Buckley M, Ferguson-Smith MA: Sequence variation and size ranges ofCAGrepeats in the Machado-Joseph disease, spinocerebellar ataxia type 1 and androgen receptor genes. Hum Mol Genet 4: 1585–1590, 1995Google Scholar
  19. 19.
    Choong CS, Kemppainen JA, Wilson EM: Evolution of the primate androgen receptor: A structural basis for disease. J Mol Evol 47: 334–342, 1998Google Scholar
  20. 20.
    Rubinsztein DC, Leggo J, Goodburn S, Barton DE, Ferguson-Smith MA: Haplotype analysis of the delta 2642 and (CAG)n polymorphisms in the Huntington's disease (HD) gene provides an explanation for an apparent 'founder'HDhaplotype. HumMol Genet 4: 203–206, 1995Google Scholar
  21. 21.
    La Spada AR, Wilson EM, Lubahn DB, Harding AE, Fischbeck KH: Androgen receptor gene mutations in X-linked spinal and bulbar muscular atrophy. Nature 352: 77–79, 1991Google Scholar
  22. 22.
    La Spada AR, Roling DB, Harding AE, Warner CL, Spiegel R, Hausmanowa-Petrusewicz I, Yee WC, Fischbeck KH: Meiotic stability and genotype-phenotype correlation of the trinucleotide repeat in X-linked spinal and bulbar muscular atrophy. Nat Genet 2: 301–304, 1992Google Scholar
  23. 23.
    Arbizu T, Santamaria J, Gomez JM, Quilez A, Serra JP: A family with adult spinal and bulbar muscular atrophy, X-linked inheritance and associated testicular failure. J Neurol Sci 59: 371–382, 1983Google Scholar
  24. 24.
    Nagashima T, Seko K, Hirose K, Mannen T, Yoshimura S, Arima R, Nagashima K, Morimatsu Y: Familial bulbospinal muscular atrophy associated with testicular atrophy and sensory neuropathy (Kennedy-Alter-Sung syndrome). Autopsy case report of two brothers. J Neurol Sci 87: 141–152, 1988Google Scholar
  25. 25.
    Mhatre AN, Trifiro MA, Kaufman M, Kazemi-Esfarjani P, Figlewicz D, Rouleau G, Pinsky L: Reduced transcriptional regulatory competence of the androgen receptor in X-linked spinal and bulbar muscular atrophy. Nat Genet 5: 184–188, 1993Google Scholar
  26. 26.
    Chamberlain NL, Driver ED, Miesfeld RL: The length and location of CAG trinucleotide repeats in the androgen receptor N-terminal domain affect transactivation function. Nucleic Acids Res 22: 3181–3186, 1994Google Scholar
  27. 27.
    Kazemi-Esfarjani P, Trifiro MA, Pinsky L: Evidence for a repressive function of the long polyglutamine tract in the human androgen receptor: Possible pathogenetic relevance for the (CAG)n-expanded neuronopathies. HumMol Genet 4: 523–527, 1995Google Scholar
  28. 28.
    Tut TG, Ghadessy FJ, Trifiro MA, Pinsky L, Yong EL: Long polyglutamine tracts in the androgen receptor are associated with reduced trans-activation, impaired sperm production, and male infertility. J Clin Endocrinol Metab 82: 3777–3782, 997Google Scholar
  29. 29.
    Irvine RA, Ma H, Yu MC, Ross RK, Stallcup MR, Coetzee GA: Inhibition of p160–mediated coactivation with increasing androgen receptor polyglutamine length. Hum Mol Genet 9: 267–274, 2000Google Scholar
  30. 30.
    Beilin J, Ball EM, Favaloro JM, Zajac JD: Effect of the androgen receptor CAG repeat polymorphism on transcriptional activity: Specificity in prostate and nonprostate cell lines. J Mol Endocrinol 25: 85–96, 2000Google Scholar
  31. 31.
    Pratt WB, Toft DO: Steroid receptor interactions with heat shock protein and immunophilin chaperones. Endocr Rev 18: 306–360, 1997Google Scholar
  32. 32.
    Jenster G, Spencer TE, Burcin MM, Tsai SY, Tsai MJ, O'Malley BW: Steroid receptor induction of gene transcription: A two-step model. Proc Natl Acad Sci USA 94: 7879–7884, 1997Google Scholar
  33. 33.
    Tyagi RK, Lavrovsky Y, Ahn SC, Song CS, Chatterjee B, Roy AK: Dynamics of intracellular movement and nucleocytoplasmic recycling of the ligand-activated androgen receptor in living cells. Mol Endocrinol 14: 1162–1174, 2000Google Scholar
  34. 34.
    Mader S, Leroy P, Chen JY, Chambon P: Multiple parameters control the selectivity of nuclear receptors for their response elements. Selectivity and promiscuity in response element recognition by retinoic acid receptors and retinoid X receptors. J Biol Chem 268: 591–600, 1993Google Scholar
  35. 35.
    Schoenmakers E, Alen P, Verrijdt G, Peeters B, Verhoeven G, Rombauts W, Claessens F: Differential DNA binding by the androgen and glucocorticoid receptors involves the second Zn-finger and a C-terminal extension of the DNA-binding domains. Biochem J 341: 515–521, 1999Google Scholar
  36. 36.
    Schoenmakers E, Verrijdt G, Peeters B, Verhoeven G, Rombauts W, Claessens F: Differences in DNA binding characteristics of the androgen and glucocorticoid receptors can determine hormone-specific responses. J Biol Chem 275: 12290–12297, 2000Google Scholar
  37. 37.
    Luisi BF, Xu WX, Otwinowski Z, Freedman LP, Yamamoto KR, Sigler PB: Crystallographic analysis of the interaction of the glucocorticoid receptor with DNA. Nature 352: 497–505, 1991Google Scholar
  38. 38.
    Rastinejad F, Perlmann T, Evans RM, Sigler PB: Structural determinants of nuclear receptor assembly on DNA direct repeats. Nature 375: 203–211, 1995Google Scholar
  39. 39.
    Gronemeyer H, Moras D: Nuclear receptors. How to finger DNA. Nature 375: 190–191, 1995Google Scholar
  40. 40.
    Reid KJ, Hendy SC, Saito JL, Sorensen P, Nelson CC: Two classes of androgen receptor elements mediate cooperativity through allosteric interactions. J Biol Chem 2000Google Scholar
  41. 41.
    Coetzee GA, Ross RK: Re: Prostate cancer and the androgen receptor. J Natl Cancer Inst 86: 872–873, 1994Google Scholar
  42. 42.
    Irvine RA, Yu MC, Ross RK, Coetzee GA: The CAG and GGC microsatellites of the androgen receptor gene are in linkage disequilibrium in men with prostate cancer. Cancer Res 55: 1937–1940, 1995Google Scholar
  43. 43.
    Ingles SA, Ross RK, Yu MC, Irvine RA, La Pera G, Haile RW, Coetzee GA: Association of prostate cancer risk with genetic polymorphisms in vitamin D receptor and androgen receptor. J Natl Cancer Inst 89: 166–170, 1997Google Scholar
  44. 44.
    Hakimi JM, Schoenberg MP, Rondinelli RH, Piantadosi S, Barrack ER: Androgen receptor variants with short glutamine or glycine repeats may identify unique subpopulations of men with prostate cancer. Clin Cancer Res 3: 1599–1608, 1997Google Scholar
  45. 45.
    Hardy DO, Scher HI, Bogenreider T, Sabbatini P, Zhang ZF, Nanus DM, Catterall JF: Androgen receptor CAG repeat lengths in prostate cancer: Correlation with age of onset. J Clin Endocrinol Metab 81: 4400–4405, 1996Google Scholar
  46. 46.
    Stanford JL, Just JJ, Gibbs M, Wicklund KG, Neal CL, Blumenstein BA, Ostrander EA: Polymorphic repeats in the androgen receptor gene: Molecular markers of prostate cancer risk. Cancer Res 57: 1194–1198, 1997Google Scholar
  47. 47.
    Hsing AW, Gao YT, Wu G, Wang X, Deng J, Chen YL, Sesterhenn IA, Mostofi FK, Benichou J, Chang C: Polymorphic CAG and GGN repeat lengths in the androgen receptor gene and prostate cancer risk: A population-based case-control study in China. Cancer Res 60: 5111–5116, 2000Google Scholar
  48. 48.
    So CW, Dong S, So CK, Cheng GX, Huang QH, Chen SJ, Chan LC: The impact of differential binding of wild-type RARalpha, PML-. Leukemia 14: 77–83, 2000Google Scholar
  49. 49.
    Ekman P, Gronberg H, Matsuyama H, Kivineva M, Bergerheim US, Li C: Links between genetic and environmental factors and prostate cancer risk. Prostate 39: 262–268, 1999Google Scholar
  50. 50.
    Edwards SM, Badzioch MD, Minter R, Hamoudi R, Collins N, Ardern-Jones A, Dowe A, Osborne S, Kelly J, Shearer R, Easton DF, Saunders GF, Dearnaley DP, Eeles RA: Androgen receptor polymorphisms: Association with prostate cancer risk, relapse and overall survival. Int J Cancer 84: 458–465, 1999Google Scholar
  51. 51.
    Correa-Cerro L, Wohr G, Haussler J, Berthon P, Drelon E, Mangin P, Fournier G, Cussenot O, Kraus P, Just W, Paiss T, Cantu JM, Vogel W: (CAG)nCAA and GGN repeats in the human androgen receptor gene are not associated with prostate cancer in a French-German population. Eur J Hum Genet 7: 357–362, 1999Google Scholar
  52. 52.
    Bratt O, Borg A, Kristoffersson U, Lundgren R, Zhang QX, Olsson H: CAGrepeat length in the androgen receptor gene is related to age at diagnosis of prostate cancer and response to endocrine therapy, but not to prostate cancer risk. Br J Cancer 81: 672–676, 1999Google Scholar
  53. 53.
    Lange EM, Chen H, Brierley K, Livermore H, Wojno KJ, Langefeld CD, Lange K, Cooney KA: The polymorphic exon 1 androgen receptor CAG repeat in men with a potential inherited predisposition to prostate cancer. Cancer Epidemiol Biomarkers Prev 9: 439–442, 2000Google Scholar
  54. 54.
    Nam RK, Elhaji Y, Krahn MD, Hakimi J, Ho M, Chu W, Sweet J, Trachtenberg J, Jewett MA, Narod SA: Significance of the cag repeat polymorphism of the androgen receptor gene in prostate cancer progression. J Urol 164: 567–572, 2000Google Scholar
  55. 55.
    Latil AG, Azzouzi R, Cancel GS, Guillaume EC, Cochan-Priollet B, Berthon PL, Cussenot O: Prostate carcinoma risk and allelic variants of genes involved in androgen biosynthesis and metabolism pathways. Cancer 92: 1130–1137, 2001Google Scholar
  56. 56.
    Modugno F, Weissfeld JL, Trump DL, Zmuda JM, Shea P, Cauley JA, Ferrell RE: Allelic variants of aromatase and the androgen and estrogen receptors: Toward a multigenic model of prostate cancer risk. Clin Cancer Res 7: 3092–3096, 2001Google Scholar
  57. 57.
    Miller EA, Stanford JL, Hsu L, Noonan E, Ostrander EA: Polymorphic repeats in the androgen receptor gene in highrisk sibships. Prostate 48: 200–205, 2001Google Scholar
  58. 58.
    Panz VR, Joffe BI, Spitz I, Lindenberg T, Farkas A, Haffejee M: Tandem CAGrepeats of the androgen receptor gene and prostate cancer risk in black and white men. Endocrine 15: 213–216, 2001Google Scholar
  59. 59.
    Butler R, Leigh PN, McPhaul MJ, Gallo JM: Truncated forms of the androgen receptor are associated with polyglutamine expansion in X-linked spinal and bulbar muscular atrophy. Hum Mol Genet 7: 121–127, 1998Google Scholar
  60. 60.
    Hsiao PW, Lin DL, Nakao R, Chang C: The linkage of Kennedy's neuron disease to ARA24, the first identified androgen receptor polyglutamine region-associated coactivator. J Biol Chem 274: 20229–20234, 1999Google Scholar
  61. 61.
    Rush MG, Drivas G, D'Eustachio P: The small nuclear GTPase Ran: How much does it run? Bioessays 18: 103–112, 1996Google Scholar
  62. 62.
    Zhang L, Leeflang EP, Yu J, Arnheim N: Studying human mutations by sperm typing: Instability of CAG trinucleotide repeats in the human androgen receptor gene. Nat Genet 7: 531–535, 1994Google Scholar
  63. 63.
    Lu S, Tsai SY, Tsai MJ: Molecular mechanisms of androgen-independent growth of human prostate cancer LNCaP-AI cells. Endocrinology 140: 5054–5059, 1999Google Scholar
  64. 64.
    Platz EA, Giovannucci E, Dahl DM, Krithivas K, Hennekens CH, Brown M, Stampfer MJ, Kantoff PW: The androgen receptor gene GGN microsatellite and prostate cancer risk. Cancer Epidemiol Biomarkers Prev 7: 379–384, 1998Google Scholar
  65. 65.
    Tilley WD, Lim-Tio SS, Horsfall DJ, Aspinall JO, Marshall VR, Skinner JM: Detection of discrete androgen receptor epitopes in prostate cancer by immunostaining: Measurement by color video image analysis. Cancer Res 54: 4096–4102, 1994Google Scholar
  66. 66.
    Prins GS, Sklarew RJ, Pertschuk LP: Image analysis of androgen receptor immunostaining in prostate cancer accurately predicts response to hormonal therapy. J Urol 159: 641–649, 1998Google Scholar
  67. 67.
    Sadi MV, Barrack ER: Image analysis of androgen receptor immunostaining in metastatic prostate cancer. Heterogeneity as a predictor of response to hormonal therapy. Cancer 71: 2574–2580, 1993Google Scholar
  68. 68.
    Takeda H, Akakura K, Masai M, Akimoto S, Yatani R, Shimazaki J: Androgen receptor content of prostate carcinoma cells estimated by immunohistochemistry is related to prognosis of patients with stage D2 prostate carcinoma. Cancer 77: 934–940, 1996Google Scholar
  69. 69.
    Pertschuk LP, Schaeffer H, Feldman JG, Macchia RJ, Kim YD, Eisenberg K, Braithwaite LV, Axiotis CA, Prins G, Green GL: Immunostaining for prostate cancer androgen receptor in paraffin identifies a subset of men with a poor prognosis. Lab Invest 73: 302–305, 1995Google Scholar
  70. 70.
    Pertschuk LP, Macchia RJ, Feldman JG, Brady KA, Levine M, Kim DS, Eisenberg KB, Rainford E, Prins GS, Greene GL: Immunocytochemical assay for androgen receptors in prostate cancer: A prospective study of 63 cases with long-term follow-up. Ann Surg Oncol 1: 495–503, 1994Google Scholar
  71. 71.
    Sweat SD, Pacelli A, Bergstralh EJ, Slezak JM, Bostwick DG: Androgen receptor expression in prostatic intraepithelial neoplasia and cancer. J Urol 161: 1229–1232, 1999Google Scholar
  72. 72.
    Kattan MW, Wheeler TM, Scardino PT: Postoperative nomogram for disease recurrence after radical prostatectomy for prostate cancer. J Clin Oncol 17: 1499–1507, 1999Google Scholar
  73. 73.
    Henshall SM, Quinn DI, Lee CS, Head DR, Golovsky D, Brenner PC, Delprado W, Stricker PD, Grygiel JJ, Sutherland RL: Altered expression of androgen receptor in the malignant epithelium and adjacent stroma is associated with early relapse in prostate cancer. Cancer Res 61: 423–427, 2001Google Scholar
  74. 74.
    Koivisto P, Kononen J, Palmberg C, Tammela T, Hyytinen E, Isola J, Trapman J, Cleutjens K, Noordzij A, Visakorpi T, Kallioniemi OP: Androgen receptor gene amplification: A possible molecular mechanism for androgen deprivation therapy failure in prostate cancer. Cancer Res 57: 314–319, 1997Google Scholar
  75. 75.
    Jarrard DF, Kinoshita H, Shi Y, Sandefur C, Hoff D, Meisner LF, Chang C, Herman JG, Isaacs WB, Nassif N: 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, 1998Google Scholar
  76. 76.
    Kinoshita H, Shi Y, Sandefur C, Meisner LF, Chang C, Choon A, Reznikoff CR, Bova GS, Friedl A, Jarrard DF: Methylation of the androgen receptor minimal promoter silences transcription in human prostate cancer. Cancer Res 60: 3623–3630, 2000Google Scholar
  77. 77.
    Yeap BB, Krueger RG, Leedman PJ: Differential posttranscriptional regulation of androgen receptor gene expression by androgen in prostate and breast cancer cells. Endocrinology 140: 3282–3291, 1999Google Scholar
  78. 78.
    Wen Y, Hu MC, Makino K, Spohn B, Bartholomeusz G, Yan DH, Hung MC: HER-2/neu promotes androgenindependent survival and growth of prostate cancer cells through the Akt pathway. Cancer Res 60: 6841–6845, 2000Google Scholar
  79. 79.
    Ruohola JK, Valve EM, Karkkainen MJ, Joukov V, Alitalo K, Harkonen PL: Vascular endothelial growth factors are differentially regulated by steroid hormones and antiestrogens in breast cancer cells. Mol Cell Endocrinol 149: 29–40, 1999Google Scholar
  80. 80.
    Goldberg YP, Kalchman MA, Metzler M, Nasir J, Zeisler J, Graham R, Koide HB, O'Kusky J, Sharp AH, Ross CA, Jirik F, Hayden MR: Absence of disease phenotype and intergenerational stability of the CAG repeat in transgenic mice expressing the human Huntington disease transcript. Hum Mol Genet 5: 177–185, 1996Google Scholar
  81. 81.
    Lu S, Tsai SY, Tsai MJ: Regulation of androgen-dependent prostatic cancer cell growth: Androgen regulation of CDK2, CDK4, and CKI p16 genes. Cancer Res 57: 4511–4516, 1997Google Scholar
  82. 82.
    Bubendorf L, Kononen J, Koivisto P, Schraml P, Moch H, Gasser TC, Willi N, Mihatsch MJ, Sauter G, Kallioniemi OP: Survey of gene amplifications during prostate cancer progression by high-throughout fluorescence in situ hybridization on tissue microarrays. Cancer Res 59: 803–806, 1999Google Scholar
  83. 83.
    Koivisto PA, Helin HJ: Androgen receptor gene ampli-fication increases tissue PSA protein expression in hormone-refractory prostate carcinoma. J Pathol 189: 219–223, 1999Google Scholar
  84. 84.
    Jenster G: Ligand-independent activation of the androgen receptor in prostate cancer by growth factors and cytokines. J Pathol 191: 227–228, 2000Google Scholar
  85. 85.
    Buchanan G, Greenberg NM, Scher HI, Harris JM, Marshall VR, Tilley WD: Collocation of androgen receptor gene mutations in prostate cancer. Clin Cancer Res 7: 1273–1281, 2001Google Scholar
  86. 86.
    Grossmann ME, Huang H, Tindall DJ: Androgen receptor signaling in androgen-refractory prostate cancer. J Natl Cancer Inst 93: 1687–1697, 2001Google Scholar
  87. 87.
    Wong CI, Zhou ZX, Sar M, Wilson EM: Steroid requirement for androgen receptor dimerization and DNA binding. Modulation by intramolecular interactions between the NH2–terminal and steroid-binding domains. J Biol Chem 268: 19004–19012, 1993Google Scholar
  88. 88.
    Quarmby VE, Beckman WCJ, Cooke DB, Lubahn DB, Joseph DR, Wilson EM, French FS: Expression and localization of androgen receptor in the R-3327 Dunning rat prostatic adenocarcinoma. Cancer Res 50: 735–739, 1990Google Scholar
  89. 89.
    Tilley WD, Wilson CM, Marcelli M, McPhaul MJ: Androgen receptor gene expression in human prostate carcinoma cell lines. Cancer Res 50: 5382–5386, 1990Google Scholar
  90. 90.
    Culig Z, Hobisch A, Hittmair A, Peterziel H, Cato AC, Bartsch G, Klocker H: Expression, structure, and function of androgen receptor in advanced prostatic carcinoma. Prostate 35: 63–70, 1998Google Scholar
  91. 91.
    Koivisto P, Visakorpi T, Kallioniemi OP: Androgen receptor gene amplification: A novel molecular mechanism for endocrine therapy resistance in human prostate cancer. Scand J Clin Lab Invest (Suppl 226): 57–63, 1996Google Scholar
  92. 92.
    Veldscholte J, Ris-Stalpers C, Kuiper GG, Jenster G, Berrevoets C, Claassen E, van Rooij HC, Trapman J, Brinkmann AO, Mulder E: A mutation in the ligand binding domain of the androgen receptor of human LNCaP cells affects steroid binding characteristics and response to antiandrogens. Biochem Biophys Res Commun 173: 534–540, 1990Google Scholar
  93. 93.
    Zhao XY, Malloy PJ, Krishnan AV, Swami S, Navone NM, Peehl DM, Feldman D: Glucocorticoids can promote androgen-independent growth of prostate cancer cells through a mutated androgen receptor. Nat Med 6: 703–706, 2000Google Scholar
  94. 94.
    Buchanan G, Tilley WD: Androgen Receptor Structure and Function in Prostate Cancer. In: Li JJ, Darling JR, Li SA (eds) Hormonal Carcinogenesis III, Springer-Verlag, New York, 2000, pp 333–341Google Scholar
  95. 95.
    Gelmann EP: Androgen receptor mutations in prostate cancer. Cancer Treat Res 87: 285–302, 1996Google Scholar
  96. 96.
    Han G, Foster BA, Mistry S, Buchanan G, Harris JM, Tilley WD, Greenberg NM: Hormone status selects for spontaneous somatic androgen receptor variants that demonstrate specific ligand and cofactor dependent activities in autochthonous prostate cancer. J Biol Chem 276: 11204–11213, 2001Google Scholar
  97. 97.
    Wurtz JM, Bourguet W, Renaud JP, Vivat V, Chambon P, Moras D, Gronemeyer H: A canonical structure for the ligand-binding domain of nuclear receptors. Nat Struct Biol 3: 206, 1996Google Scholar
  98. 98.
    Veldscholte J, Berrevoets CA, Ris-Stalpers C, Kuiper GG, Jenster G, Trapman J, Brinkmann AO, Mulder E: The androgen receptor in LNCaP cells contains a mutation in the ligand binding domain which affects steroid binding characteristics and response to antiandrogens. J Steroid Biochem Mol Biol 41: 665–669, 1992Google Scholar
  99. 99.
    Matias PM, Donner P, Coelho R, Thomaz M, Peixoto C, Macedo S, Otto N, Joschko S, Scholz P, Wegg A, Basler S, Schafer M, Egner U, Carrondo MA: Structural evidence for ligand specificity in the binding domain of the human Androgen receptor: Implications for pathogenic gene mutations. J Biol Chem 275: 26164–26171, 2000Google Scholar
  100. 100.
    Sack JS, Kish KF, Wang C, Attar RM, Kiefer SE, An Y, Wu GY, Scheffler JE, Salvati ME, Krystek SR, Weinmann R, Einspahr HM: Crystallographic structures of the ligand-binding domains of the androgen receptor and its T877A mutant complexed with the natural agonist dihydrotestosterone. Proc Natl Acad Sci USA 98: 4904–4909, 2001Google Scholar
  101. 101.
    Tilley WD, Buchanan G, Hickey TE, Bentel JM: Mutations in the androgen receptor gene are associated with progression of human prostate cancer to androgen independence. Clin Cancer Res 2: 277–285, 1996Google Scholar
  102. 102.
    Marcelli M, Ittmann M, Mariani S, Sutherland R, Nigam R, Murthy L, Zhao Y, DiConcini D, Puxeddu E, Esen A, Eastham J, Weigel NL, Lamb DJ: Androgen receptor mutations in prostate cancer. Cancer Res 60: 944–949, 2000Google Scholar
  103. 103.
    Aarnisalo P, Santti H, Poukka H, Palvimo JJ, Janne OA: Transcription activating and repressing functions of the androgen receptor are differentially influenced by mutations in the deoxyribonucleic acid-binding domain. Endocrinology 140: 3097–3105, 1999Google Scholar
  104. 104.
    Bruggenwirth HT, Boehmer AL, Lobaccaro JM, Chiche L, Sultan C, Trapman J, Brinkmann AO: Substitution of Ala564 in the first zinc cluster of the deoxyribonucleic acid (DNA)-binding domain of the androgen receptor by Asp, Asn, or Leu exerts differential effects on DNA binding. Endocrinology 139: 103–110, 1998Google Scholar
  105. 105.
    Poujol N, Lobaccaro JM, Chiche L, Lumbroso S, Sultan C: Functional and structural analysis of R607Q and R608K androgen receptor substitutions associated with male breast cancer. Mol Cell Endocrinol 130: 43–51, 1997Google Scholar
  106. 106.
    Rundlett SE, Miesfeld RL: Quantitative differences in androgen and glucocorticoid receptor DNA binding properties contribute to receptor-selective transcriptional regulation. Mol Cell Endocrinol 109: 1–10, 1995Google Scholar
  107. 107.
    Verrijdt G, Schoenmakers E, Haelens A, Peeters B, Verhoeven G, Rombauts W, Claessens F: Change of speci-ficity mutations in androgen-selective enhancers. Evidence for a role of differential DNA binding by the androgen receptor. J Biol Chem 275: 12298–12305, 2000Google Scholar
  108. 108.
    Blanco JG, Minucci S, Lu J, Yang XJ, Walker KK, Chen H, Evans RM, Nakatani Y, Ozato K: The histone acetylase PCAF is a nuclear receptor coactivator. Genes Dev 12: 1638–1651, 1998Google Scholar
  109. 109.
    Moilanen AM, Karvonen U, Poukka H, Yan W, Toppari J, Janne OA, Palvimo JJ: A testis-specific androgen receptor coregulator that belongs to a novel family of nuclear proteins. J Biol Chem 274: 3700–3704, 1999Google Scholar
  110. 110.
    Moilanen AM, Poukka H, Karvonen U, Hakli M, Janne OA, Palvimo JJ: Identification of a novel RING finger prote in as a coregulator in steroid receptor-mediated gene transcription. Mol Cell Biol 18: 5128–5139, 1998Google Scholar
  111. 111.
    Poukka H, Karvonen U, Yoshikawa N, Tanaka H, Palvimo JJ, Janne OA: The RING finger protein SNURF modulates nuclear trafficking of the androgen receptor. J Cell Sci 113: 2991–3001, 2000Google Scholar
  112. 112.
    Chamberlain NL, Whitacre DC, Miesfeld RL: Delineation of two distinct type 1 activation functions in the androgen receptor amino-terminal domain. J Biol Chem 271: 26772–26778, 1996Google Scholar
  113. 113.
    Gao T, Marcelli M, McPhaul MJ: Transcriptional activation and transient expression of the human androgen receptor. J Steroid Biochem Mol Biol 59: 9–20, 1996Google Scholar
  114. 114.
    Schoenberg MP, Hakimi JM, Wang S, Bova GS, Epstein JI, Fischbeck KH, Isaacs WB, Walsh PC, Barrack ER: Microsatellite mutation (CAG24–>18) in the androgen receptor gene in human prostate cancer. Biochem Biophys Res Commun 198: 74–80, 1994Google Scholar
  115. 115.
    Watanabe M, Ushijima T, Shiraishi T, Yatani R, Shimazaki J, Kotake T, Sugimura T, Nagao M: Genetic alterations of androgen receptor gene in Japanese human prostate cancer. Jpn J Clin Oncol 27: 389–393, 1997Google Scholar
  116. 116.
    Wallen MJ, Linja M, Kaartinen K, Schleutker J, Visakorpi T: Androgen receptor gene mutations in hormone-refractory prostate cancer. J Pathol 189: 559–563, 1999Google Scholar
  117. 117.
    Yang M, Raynor M, Neufing PJ, Buchanan G, Tilley WD: Disruption of the polyglutamine tract results in increased ligand-induced transcriptional activity of the androgen receptor. Proc Amer Ass Canc Res 40 (Abstract 2699): 408, 1999Google Scholar
  118. 118.
    MaH, Hong H, Huang SM, Irvine RA, Webb P, Kushner PJ, Coetzee GA, Stallcup MR: Multiple signal input and output domains of the 160–kilodalton nuclear receptor coactivator proteins. Mol Cell Biol 19: 6164–6173, 1999Google Scholar
  119. 119.
    Fronsdal K, Engedal N, Slagsvold T, Saatcioglu F: CREB binding protein is a coactivator for the androgen receptor and mediates cross-talk with AP-1. J Biol Chem 273: 31853–31859, 1998Google Scholar
  120. 120.
    Kupfer SR, Marschke KB, Wilson EM, French FS: Receptor accessory factor enhances specific DNA binding of androgen and glucocorticoid receptors. J Biol Chem 268: 17519–17527, 1993Google Scholar
  121. 121.
    Gregory CW, He B, Johnson RT, Ford OH, Mohler JL, French FS, Wilson EM: A mechanism for androgen receptor-mediated prostate cancer recurrence after androgen deprivation therapy. Cancer Res 61: 4315–4319, 2001Google Scholar
  122. 122.
    Kantoff P, Giovannucci E, Brown M: The androgen receptor CAG repeat polymorphism and its relationship to prostate cancer. Biochim Biophys Acta 1378: C1–C5, 1998Google Scholar
  123. 123.
    Zhou BP, Hu MC, Miller SA, Yu Z, Xia W, Lin SY, Hung MC: HER-2/neu blocks tumor necrosis factorinduced apoptosis via the Akt/NF-kappaB pathway. J Biol Chem 275: 8027–8031, 2000Google Scholar
  124. 124.
    Signoretti S, Montironi R, Manola J, Altimari A, Tam C, Bubley G, Balk S, Thomas G, Kaplan I, Hlatky L, Hahnfeldt P, Kantoff P, Loda M: Her-2–neu expression and progression toward androgen independence in human prostate cancer. J Natl Cancer Inst 92: 1918–1925, 2000Google Scholar
  125. 125.
    Osman I, Scher HI, Drobnjak M, Verbel D, Morris M, Agus D, Ross JS, Cordon-Cardo C: HER-2/neu (p185neu) prote in expression in the natural or treated history of prostate cancer. Clin Cancer Res 7: 2643–2647, 2001Google Scholar
  126. 126.
    Craft N, Shostak Y, Carey M, Sawyers CL: A mechanism for hormone-independent prostate cancer through modulation of androgen receptor signaling by the HER-2/neu tyrosine kinase. Nat Med 5: 280–285, 1999Google Scholar
  127. 127.
    Sadar MD, Gleave ME: Ligand-independent activation of the androgen receptor by the differentiation agent butyrate in human prostate cancer cells. Cancer Res 60: 5825–5831, 2000Google Scholar
  128. 128.
    Agus DB, Scher HI, Higgins B, Fox WD, Heller G, Fazzari M, Cordon-Cardo C, Golde DW: Response of prostate cancer to anti-Her-2/neu antibody in androgendependent and-independent human xenograft models. Cancer Res 59: 4761–4764, 1999Google Scholar
  129. 129.
    Labrie F, Dupont A, Cusan L, Gomez J, Emond J, Monfette G: Combination therapy with flutamide and medical (LHRH agonist) or surgical castration in advanced prostate cancer: 7–year clinical experience. J Steroid Biochem Mol Biol 37: 943–950, 1990Google Scholar
  130. 130.
    Schmitt B, Bennett C, Seidenfeld J, Samson D, Wilt T: Maximal androgen blockade for advanced prostate cancer. Cochrane Database Syst Rev CD001526, 2000Google Scholar
  131. 131.
    Kelly WK, Slovin S, Scher HI: Steroid hormone withdrawal syndromes. Pathophysiology and clinical significance. Urol Clin North Am 24: 421–431, 1997Google Scholar
  132. 132.
    Kelly WK, Scher HI: Prostate specific antigen decline after antiandrogen withdrawal: The flutamide withdrawal syndrome. J Urol 149: 607–609, 1993Google Scholar
  133. 133.
    Small EJ, Srinivas S: The antiandrogen withdrawal syndrome. Experience in a large cohort of unselected patients with advanced prostate cancer. Cancer 76: 1428–1434, 1995Google Scholar
  134. 134.
    Huan SD, Gerridzen RG, Yau JC, Stewart DJ: Antiandrogen withdrawal syndrome with nilutamide. Urology 49: 632–634, 1997Google Scholar
  135. 135.
    Nieh PT: Withdrawal phenomenon with the antiandrogen casodex. J Urol 153: 1070–1072, 1995Google Scholar
  136. 136.
    Small EJ, Carroll PR: Prostate-specific antigen decline after casodex withdrawal: Evidence for an antiandrogen withdrawal syndrome. Urology 43: 408–410, 1994Google Scholar
  137. 137.
    Bissada NK, Kaczmarek AT: Complete remission of hormone refractory adenocarcinoma of the prostate in response to withdrawal of diethylstilbestrol. J Urol 153: 1944–1945, 1995Google Scholar
  138. 138.
    Dawson NA, McLeod DG: Dramatic prostate specific antigen decrease in response to discontinuation of megestrol acetate in advanced prostate cancer: Expansion of the antiandrogen withdrawal syndrome. J Urol 153: 1946–1947, 1995Google Scholar
  139. 139.
    Akakura K, Akimoto S, Furuya Y, Ito H: Incidence and characteristics of antiandrogen withdrawal syndrome in prostate cancer after treatment with chlormadinone acetate. Eur Urol 33: 567–571, 1998Google Scholar
  140. 140.
    Scher HI, Kelly WK: Flutamide withdrawal syndrome: Its impact on clinical trials in hormone-refractory prostate cancer. J Clin Oncol 11: 1566–1572, 1993Google Scholar
  141. 141.
    Small EJ, Baron A, Bok R: Simultaneous antiandrogen withdrawal and treatment with ketoconazole and hydrocortisone in patients with advanced prostate carcinoma. Cancer 80: 1755–1759, 1997Google Scholar
  142. 142.
    Taplin ME, Bubley GJ, Ko YJ, Small EJ, Upton M, Rajeshkumar B, Balk SP: Selection of androgen receptor mutations in prostate cancers treated with androgen antagonists. Cancer Res 59: 2511–2515, 1999Google Scholar
  143. 143.
    Yeh S, Kang HY, Miyamoto H, Nishimura K, Chang HC, Ting HJ, Rahman M, Lin HK, Fujimoto N, Hu YC, Mizokami A, Huang KE, Chang C: Differential induction of androgen receptor transactivation by different androgen receptor coactivators in human prostate cancer DU145 cells. Endocrine 11: 195–202, 1999Google Scholar

Copyright information

© Kluwer Academic Publishers 2001

Authors and Affiliations

  • Grant Buchanan
    • 1
  • Ryan A. Irvine
    • 2
  • Gerhard A. Coetzee
    • 2
  • Wayne D. Tilley
    • 1
  1. 1.Department of MedicineUniversity of Adelaide and Hanson InstituteAdelaideAustralia
  2. 2.Departments of Urology and Preventive MedicineUniversity of Southern California Keck School of Medicine, Norris Cancer CenterLos AngelesUSA

Personalised recommendations