Androgen regulation of prostate cancer: Where are we now?

Journal of Endocrinological Investigation

Volumn 34, Issue 3, 2011, Pages 232-243

  Corona, G ^a,b   Baldi, E ^a   Maggi, Mario ^a  

^a UNIVERSITY OF FLORENCE   (Italy)

^b BELLARIA HOSPITAL   (Italy)

Author keywords

Androgen deprivation therapy; Cardiovascular risk; Osteoporosis; Prostate; Testosterone

Indexed keywords

ABIRATERONE ACETATE; ANDROGEN; ANDROGEN RECEPTOR; BICALUTAMIDE; DUTASTERIDE; FINASTERIDE; GONADORELIN AGONIST; GONADORELIN ANTAGONIST; PLACEBO; STEROID 5ALPHA REDUCTASE; STEROID 5ALPHA REDUCTASE INHIBITOR; TESTOSTERONE;

ADVANCED CANCER; ANDROGEN DEFICIENCY; ANDROGEN DEPRIVATION THERAPY; ANDROGEN SYNTHESIS; BODY FAT DISTRIBUTION; BONE METABOLISM; CANCER CELL; CANCER GROWTH; CANCER RISK; CARCINOGENESIS; CARDIOVASCULAR RISK; CELL DIFFERENTIATION; DIABETES MELLITUS; DYSLIPIDEMIA; FRACTURE; HUMAN; HYPOGONADISM; INSULIN RESISTANCE; INSULIN SENSITIVITY; LIPID METABOLISM; MEDICAL LITERATURE; MEDLINE; MORBIDITY; MORTALITY; NONHUMAN; OBESITY; OSTEOPOROSIS; PALLIATIVE THERAPY; PATHOPHYSIOLOGY; PROSTATE CANCER; PROSTATE HYPERTROPHY; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SIGNAL TRANSDUCTION; SUPPLEMENTATION; SYSTEMATIC REVIEW; UPREGULATION;

5-ALPHA REDUCTASE INHIBITORS; ANDROGENS; CLINICAL TRIALS AS TOPIC; HUMANS; MALE; PROSTATE; PROSTATIC NEOPLASMS; RECEPTORS, ANDROGEN;

EID: 79957902488     PISSN: 03914097     EISSN: 17208386     Source Type: Journal    
DOI: 10.3275/7501     Document Type: Review

References (132)

1. Fibbi B, Penna G, Morelli A, Adorini L, Maggi M. Chronic inflammation in the pathogenesis of benign prostatic hyperplasia. Int J Androl 2010, 33: 475-88.
2. rd ed. Cambridge: Cambridge University Press. 2004, 347-74.
3. Lippman SM, Klein EA, Goodman PJ, et al. Effect of selenium and vitamin E on risk of PC and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA 2009, 301: 39-51.
4. D'Amico A, Chen M, Roehl K, Catalona W. Preoperative PSA velocity and the risk of death from PC after radical prostatectomy. N Engl J Med 2004, 351: 125-35.
5. Roehrborn CG. Pathology of benign prostatic hyperplasia. Int J Impot Res 2008, 20 (Suppl 3): S11-8.
6. Behre HM, Bohmeyer J, Nieschlag E. Prostate volume in testosterone-treated and untreated hypogonadal men in comparison to age-matched normal controls. Clin Endocrinol (Oxf) 1994, 40: 341-9. (Pubitemid 24194627)
7. Huggins C, Hodges CV. Studies on prostatic cancer. The effect of castration, of estrogen and of androgen injection on serum phosphatase in metastatic carcinoma of the prostate. Cancer Res 1941, 1:293-7.
8. Sharifi N. New agents and strategies for the hormonal treatment of castration-resistant prostate cancer. Expert Opin Investig Drugs 2010, 19: 837-46.
9. Shah S, Ryan C. Abiraterone acetate for castration resistant prostate cancer. Expert Opin Investig Drugs 2010, 19: 563-70.
10. Laufer M, Denmeade SR, Sinibaldi VJ, Carducci MA, Eisenberger MA. Complete androgen blockade for prostate cancer: what went wrong? J Urol 2000, 164: 3-9. (Pubitemid 30434247)
11. Bubley GJ, Carducci M, Dahut W, et al. Eligibility and response guidelines for phase II clinical trials in androgen-independent prostate cancer: recommendations from the Prostate-Specific Antigen Working Group. J Clin Oncol 1999, 17: 3461-7. (Pubitemid 29517916)
12. Page ST, Lin DW, Mostaghel EA, et al. Persistent intraprostatic androgen concentrations after medical castration in healthy men. J Clin Endocrinol Metab 2006, 91: 3850-6. (Pubitemid 44536854)
13. Wilson JD. Recent studies on the mechanism of action of testosterone. N Engl J Med 1972, 287: 1284-91.
14. Zhu YS, Imperato-McGinley JL 5alpha-reductase isozymes and androgen actions in the prostate. Ann NY Acad Sci 2009, 1155: 43-56.
15. Raynaud JP. Prostate cancer risk in testosterone-treated men. J Steroid Biochem Mol Biol. 2006, 102: 261-6.
16. Gravas S, Oelke M. Current status of 5alpha-reductase inhibitors in the management of lower urinary tract symptoms and BPH. World J Urol 2010, 28: 9-15.
17. Thompson IM, Goodman PJ, Tangen CM, et al. The influence of finasteride on the development of PC. N Engl J Med 2003, 349: 215-24.
18. Andriole GL, Bostwick DG, Brawley OW et al; REDUCE Study Group. Effect of dutasteride on the risk of prostate cancer. N Engl J Med 2010, 362: 1192-202.
19. Strope SA, Andriole GL. Update on chemoprevention for prostate cancer. Curr Opin Urol 2010, 20: 194-7.
20. Walsh PC. Chemoprevention of prostate cancer. N Engl J Med 2010, 362: 1237-8.
21. Adorini L, Penna G, Fibbi B, Maggi M. Vitamin D receptor agonists target static, dynamic, and inflammatory components of benign prostatic hyperplasia. Ann NY Acad Sci 2010, 1193: 146-52.
22. Crescioli C, Ferruzzi P, Caporali A, et al. Inhibition of spontaneous and androgen-induced prostate growth by a nonhypercalcemic calcitriol analog. Endocrinology 2003, 144: 3046-57. (Pubitemid 36819907)
23. Morgentaler A, Traish AM. Shifting the paradigm of testosterone and prostate cancer: the saturation model and the limits of androgen-dependent growth. Eur Urol 2009, 55: 310-21.
24. Corona G, Boddi V, Lotti F, et al. The relationship of testosterone to prostate-specific antigen in men with sexual dysfunction. J Sex Med 2010, 7: 284-92.
25. Wu FC, Tajar A, Beynon JM, et al; EMAS Group. Identification of late-onset hypogonadism in middle-aged and elderly men. N Engl J Med 2010, 363: 123-35.
26. Gacci M, Corona G, Apolone G, et al. Influence of serum testosterone on urinary continence and sexual activity in patients undergoing radical prostatectomy for clinically localized prostate cancer. Prostate Cancer Prostatic Dis 2010, 13: 168-72.
27. Takizawa I, Nishiyama T, Hara N, Isahaya E, Hoshii T, Takahashi K. Serum prostate-specific antigen levels reflect the androgen milieu in patients with localized prostate cancer receiving androgen deprivation therapy: Tumor malignant potential and androgen milieu. Prostate 2010, 70: 1395-401.
28. van Aubel OG, Bolt-de Vries J, Blankenstein MA, de Jong FH, Schröder FH. Circulating testosterone, prostatic nuclear androgen receptor and time to progression in patients with metastatic disease of the prostate treated by orchiectomy. Urol Res 1989, 17: 99-102. (Pubitemid 19102603)
29. Sher DJ, Mantzoros C, Jacobus S, Regan MM, Lee GS, Oh WK. Absence of relationship between steroid hormone levels and prostate cancer tumor grade. Urology 2009, 73: 356-61.
30. Travis RC, Key TJ, Allen NE, et al. Serum androgens and prostate cancer among 643 cases and 643 controls in the European Prospective Investigation into Cancer and Nutrition. Int J Cancer 2007, 121: 1331-8. (Pubitemid 47293802)
31. Folkerd EJ, Dowsett M. Influence of sex hormones on cancer progression. J Clin Oncol 2010, 28: 4038-44.
32. Roddam AW, Allen NE, Appleby P, Key TJ; Endogenous Hormones and Prostate Cancer Collaborative Group. Endogenous sex hormones and prostate cancer: a collaborative analysis of 18 prospective studies. J Natl Cancer Inst 2008, 100: 170-83. (Pubitemid 351480553)
33. Fernández-Balsells MM, Murad MH, Lane M, et al. Adverse effects of testosterone therapy in adult men: a systematic review and metaanalysis. J Clin Endocrinol Metab 2010, 95: 2560-75.
34. Marks LS, Mazer NA, Mostaghel E, et al. Effect of testosterone replacement therapy on prostate tissue in men with late-onset hypogonadism: a randomized controlled trial. JAMA 2006, 296: 2351-61. (Pubitemid 44749363)
35. Lindström S, Ma J, Altshuler D, et al. A large study of androgen receptor germline variants and their relation to sex hormone levels and prostate cancer risk. Results from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium. J Clin Endocrinol Metab 2010, 95: E121-7.
36. Severi G, Morris HA, Maclnnis RJ, et al. Circulating steroid hormones and the risk of prostate cancer. Cancer Epidemiol Biomarkers Prev 2006, 15: 86-91.
37. Sofikerim M, Eskicorapci S, Oruç O, Ozen H. Hormonal predictors of prostate cancer. Urol Int 2007, 79: 13-8.
38. Massengill JC, Sun L, Moul JW, et al. Pretreatment total T level predicts pathological stage in patients with localized prostate cancer treated with radical prostatectomy. J Urol 2003, 169: 1670-5. (Pubitemid 36443468)
39. Imamoto T, Suzuki H, Fukasawa S, et al. Pretreatment serum T level as a predictive factor of pathological stage in localized prostate cancer patients treated with radical prostatectomy. Eur Urol 2005, 47: 308-12. (Pubitemid 40248848)
40. Isom-Batz G, Bianco FJ Jr, Kattan MW, Mulhall JP, Lilja H, Eastham JA. T as a predictor of pathological stage in clinically localized prostate cancer. J Urol 2005, 173: 1935-7. (Pubitemid 40675215)
41. Morgentaler A, Rhoden EL. Prevalence of prostate cancer among hypogonadal men with prostate-specific antigen levels of 4.0 ng/mL or less. Urology 2006, 68: 1263-7. (Pubitemid 44880344)
42. Isbarn H, Pinthus JH, Marks LS, et al. Testosterone and prostate cancer: revisiting old paradigms. Eur Urol 2009, 56: 48-56.
43. Eikenberry SE, Nagy JD, Kuang Y. The evolutionary impact of androgen levels on prostate cancer in a multi-scale mathematical model. Biol Direct 2010, 5: 24.
44. Iversen P, Rasmussen F, Christensen IJ. Serum T as a prognostic factor in patients with advanced prostatic carcinoma. Scand J Urol Nephrol Suppl 1994, 157: 41-7. (Pubitemid 24205646)
45. Kaufman JM, Graydon RJ. Androgen replacement after curative radical prostatectomy for prostate cancer in hypogonadal men. J Urol 2004, 172: 920-2. (Pubitemid 39096423)
46. Agarwal PK, Oefelein MG. Testosterone replacement therapy after primary treatment for prostate cancer. J Urol 2005, 173: 533-6.
47. Khera M, Grober ED, Najari B, et al. Testosterone replacement therapy following radical prostatectomy. J Sex Med 2009, 6: 1165-70.
48. Leibowitz RL, Dorff TB, Tucker S, Symanowski J, Vogelzang NJ. Testosterone replacement in prostate cancer survivors with hypogonadal symptoms. BJU Int 2010, 105: 1397-401.
49. Davilla H, Arison C, Hall M, Salup R, Lockhart J, Carrion R. Analysis of the PSA response after testosterone supplementation in patients who previously received management for their localized prostate cancer. J Urol Suppl 2008, 179 (Suppl 4): 428 (abs. 1247).
50. Nabulsi O, Tal R, Gotto G, Narus J, Goldenberg L, Mulhall JP. Outcomes analysis of testosterone supplementation in hypogonadal men following radical prostatectomy. J Urol Suppl 2008, 179 (Suppl 4): 406 (abs. 1244).
51. Morales A, Black AM, Emerson LE. Testosterone administration to men with testosterone deficiency syndrome after external beam radiotherapy for localized prostate cancer: preliminary observations. BJU Int 2009, 103: 62-4.
52. Sarosdy MF. Testosterone replacement for hypogonadism after treatment of early prostate cancer with brachytherapy. Cancer 2007, 109: 536-41. (Pubitemid 46190961)
53. Wang C, Nieschlag E, Swerdloff R, et al. International Society of Andrology (ISA); International Society for the Study of Aging Male (ISSAM); European Association of Urology (EAU); European Academy of Andrology (EAA); American Society of Andrology (ASA). Investigation, treatment, and monitoring of late-onset hypogonadism in males: ISA, ISSAM, EAU, EAA, and ASA recommendations. J Androl 2009, 30: 1-9.
54. Buvat J, Maggi M, Gooren L, et al. Endocrine aspects of male sexual dysfunctions. J Sex Med 2010, 7: 1627-56.
55. Shahinian VB, Kuo YF, Freeman JL, Orihuela E, Goodwin JS. Increasing use of gonadotropin-releasing hormone agonists for the treatment of localized prostate carcinoma. Cancer 2005; 103: 1615-24.
56. Smith MR. Androgen deprivation therapy for prostate cancer: new concepts and concerns. Curr Opin Endocrinol Diabetes Obes 2007, 14: 247-54. (Pubitemid 46684481)
57. Isbarn H, Boccon-Gibod L, Carroll PR, et al. Androgen Deprivation Therapy for the treatment of prostate cancer: consider both benefits and risks. Eur Urol 2009, 55: 62-75.
58. Shahani S, Braga-Basaria M, Basaria S. Androgen Deprivation Therapy in prostate cancer and metabolic risk for atherosclerosis. J Clin Endocrinol Metab 2008, 93: 2042-9. (Pubitemid 351831513)
59. Saylor PJ, Smith MR. Metabolic complications of Androgen Deprivation Therapy for prostate cancer. J Urol 2009, 181: 1998-2008.
60. Basaria S. Androgen deprivation therapy, insulin resistance, and cardiovascular mortality: an inconvenient truth. J Androl 2008, 29: 534-9.
61. Serpa Neto A, Tobias-Machado M, Esteves MA, et al. A systematic review and meta-analysis of bone metabolism in prostate adenocarcinoma. BMC Urol 2010, 10: 9.
62. Brufsky AM. Cancer treatment-induced bone loss: pathophysiology and clinical perspectives. Oncol 2008, 13: 187-95. (Pubitemid 351342583)
63. Basaria S, Lieb J 2nd, Tang A, et al. Long-term effects of androgen deprivation therapy in prostate cancer patients. Clin Endocrinol (Oxf) 2002, 56: 779.
64. Smith JC, Bennett S, Evans LM, et al. The effects of induced hypogonadism on arterial stiffness, body composition, and metabolic parameters in males with prostate cancer. J Clin Endocrinol Metab 2001, 86: 4261-7. (Pubitemid 32848544)
65. Smith MR, Finkelstein JS, McGovern FJ, et al. Changes in body composition during androgen deprivation therapy for prostate cancer. J Clin Endocrinol Metab 2002, 87: 599-603. (Pubitemid 34158224)
66. Smith MR, Lee H, Nathan DM. Insulin sensitivity during combined androgen blockade for prostate cancer. J Clin Endocrinol Metab 2006, 91: 1305.
67. Chen Z, Maricic M, Nguyen P, Ahmann FR, Bruhn R, Dalkin BL. Low bone density and high percentage of body fat among men who were treated with androgen deprivation therapy for prostate carcinoma. Cancer 2002, 95: 2136-44. (Pubitemid 35253375)
68. Lee H, McGovern K, Finkelstein J, Smith MR. Changes in bone mineral density and body composition during initial and long-term gonadotropin-releasing hormone agonist treatment for prostate carcinoma. Cancer 2005, 104: 1633-7. (Pubitemid 41437426)
69. Corona G, Mannucci E, Forti G, Maggi M. Hypogonadism, ED, metabolic syndrome and obesity: a pathological link supporting cardiovascular diseases. Int J Androl 2009, 32: 587-98.
70. Traish AM, Guay A, Feeley R, Saad F. The dark side of testosterone deficiency: I. Metabolic syndrome and erectile dysfunction. J Androl 2009, 30: 10-22.
71. Corona G, Rastrelli G, Vignozzi L, Mannucci E, Maggi M. Testosterone, cardiovascular disease and the metabolic sindrome. Best Pract Res Clin Endocrinol Metab 2011, 25: 337-53.
72. Segal RJ, Reid RD, Courneya KS, et al. Resistance exercise in men receiving androgen deprivation therapy for prostate cancer. J Clin Oncol 2003, 21: 1653.
73. Corona G, Monami M, Rastrelli G, et al. Type 2 diabetes mellitus and testosterone: a meta-analysis study. Int J Androl 2010, Oct 24. doi: 10.1111/J.1365-2605.2010.01117.x. [Epub ahead of print]
74. Ding EL, Song Y, Malik VS, Liu S. Sex differences of endogenous sex hormones and risk of type 2 diabetes: a systematic review and meta-analysis. JAMA 2006, 295: 1288-99.
75. Pitteloud N, Mootha VK, Dwyer AA, et al. Relationship between testosterone levels, insulin sensitivity, and mitochondrial function in men. Diabetes Care 2005, 28: 1636-42. (Pubitemid 41340902)
76. Muller M, Grobbee DE, den Tonkelaar I, Lamberts SW, van der Schouw YT. Endogenous sex hormones and metabolic syndrome in aging men. J Clin Endocrinol Metab 2005, 90: 2618-23. (Pubitemid 40686299)
77. Yialamas MA, Dwyer AA, Hanley E, Lee H, Pitteloud N, Hayes FJ. Acute sex steroid withdrawal reduces insulin sensitivity in healthy men with idiopathic hypogonadotropic hypogonadism. J Clin Endocrinol Metab 2007, 92: 4254-9. (Pubitemid 350074740)
78. Dockery F, Bulpitt CJ, Agarwal S, Donaldson M, Rajkumar C. Testosterone suppression in men with prostate cancer leads to an increase in arterial stiffness and hyperinsulinaemia. Clin Sci (Lond) 2003, 104: 195-201. (Pubitemid 36238052)
79. Basaria S, Muller DC, Carducci MA, Egan J, Dobs AS. Hyperglycemia and insulin resistance in men with prostate carcinoma who receive androgen deprivation therapy. Cancer 2006, 106: 581-8. (Pubitemid 43157621)
80. Keating NL, O'Malley AJ, Smith MR. Diabetes and cardiovascular disease during androgen deprivation therapy for prostate cancer. J Clin Oncol 2006, 24: 4448-56. (Pubitemid 46630983)
81. Moorjani S, Dupont A, Labrie F, et al. Changes in plasma lipoproteins during various androgen suppression therapies in men with prostatic carcinoma: effects of orchiectomy, estrogen, and combination treatment with luteinizing hormone-releasing hormone agonist and flutamide. J Clin Endocrinol Metab 1988, 66: 314-22. (Pubitemid 18065174)
82. Braga-Basaria M, Muller DC, Carducci MA, Dobs AS, Basaria S. Lipoprotein profile in men with prostate cancer undergoing androgen deprivation therapy. Int J Impot Res 2006, 18: 494-8. (Pubitemid 44330303)
83. Saigal CS, Gore JL, Krupski TL, Hanley J, Schonlau M, Litwin MS. Androgen deprivation therapy increases cardiovascular morbidity in men with prostate cancer. Cancer 2007, 110: 1493-500. (Pubitemid 47463063)
84. D'Amico AV, Denham JW, Crook J, et al. Influence of androgen suppression therapy for prostate cancer on the frequency and timing of fatal myocardial infarctions. J Clin Oncol 2007, 25: 2420-5. (Pubitemid 46999213)
85. Tsai HK, D'Amico AV, Sadetsky N, Chen MH, Carroll PR. Androgen deprivation therapy for localized prostate cancer and the risk of cardiovascular mortality. J Natl Cancer Inst 2007, 99: 1516-24. (Pubitemid 351767235)
86. Efstathiou JA, Bae K, Shipley WU, et al. Cardiovascular mortality and duration of androgen deprivation for locally advanced prostate cancer: analysis of RTOG 92-02. Eur Urol 2008, 54: 816.
87. rd, Bae K, Speight J, et al. Short-term neoadjuvant androgen deprivation therapy and external-beam radiotherapy for locally advanced prostate cancer: long-term results of RTOG 8610. J Clin Oncol 2008, 26: 585.
88. Efstathiou JA, Bae K, Shipley WU, et al. Cardiovascular mortality after androgen deprivation therapy for locally advanced prostate cancer: RTOG 85-31. J Clin Oncol 2009, 27: 92.
89. Studer UE, Whelan P, Albrecht W, et al. Immediate or deferred androgen deprivation for patients with prostate cancer not suitable for local treatment with curative intent: European Organisation for Research and Treatment of Cancer (EORTC) Trial 30891. J Clin Oncol 2006, 24: 1868-76. (Pubitemid 46638985)
90. Nanda A, Chen MH, Braccioforte MH, Moran BJ, D'Amico AV. Hormonal therapy use for prostate cancer and mortality in men with coronary artery disease-induced congestive heart failure or myocardial infarction. JAMA 2009, 302: 866-73.
91. Hayes JH, Chen MH, Moran BJ, et al. Androgen-suppression therapy for prostate cancer and the risk of death in men with a history of myocardial infarction or stroke. BJU Int 2010, 106: 979-85.
92. Goldstein AS, Huang J, Guo C, Garraway IP, Witte ON. Identification of a cell of origin for human prostate cancer. Science 2010, 329: 568-71.
93. Bostwick DG, Shan A, Qian J, et al. Independent origin of multiple foci of prostatic intraepithelial neoplasia: comparison with matched foci of prostate carcinoma. Cancer 1998, 83: 1995-2002. (Pubitemid 28503732)
94. Craft N, Chhor C, Tran C, et al. Evidence for clonal outgrowth of androgen-independent prostate cancer cells from androgen-dependent tumors through a two-step process. Cancer Res 1999, 59: 5030-6. (Pubitemid 29472911)
95. Chen CD, Welsbie DS, Tran C, et al. Molecular determinants of resistance to antiandrogen therapy. Nat Med 2004, 10: 33-9. (Pubitemid 38524696)
96. Marques RB, van Weerden WM, Erkens-Schulze S, et al. The human PC346 xenograft and cell line panel: a model system for prostate cancer progression. Eur Urol 2006, 49: 245-57. (Pubitemid 43197860)
97. Zhou JR, Yu L, Zerbini LF, Libermann TA, Blackburn GL. Progression to androgen-independent LNCaP human prostate tumors: cellular and molecular alterations. Int J Cancer 2004, 110: 800-6. (Pubitemid 38758504)
98. Visakorpi T, Hyytinen E, Koivisto P, et al. In vivo amplification of the androgen receptor gene and progression of human prostate cancer. Nat Genet 1995, 9: 401-6.
99. Koivisto P, Kononen J, Palmberg C, et al. Androgen receptor gene amplification: a possible molecular mechanism for androgen deprivation therapy failure in prostate cancer. Cancer Res 1997, 57: 314-9. (Pubitemid 27036612)
100. Marcelli M, Ittmann M, Mariani S, et al. Androgen receptor mutations in prostate cancer. Cancer Res 2000, 60: 944-9. (Pubitemid 30129530)
101. Gregory CW, He B, Johnson RT, et al. A mechanism for androgen receptor-mediated prostate cancer recurrence after androgen deprivation therapy. Cancer Res 2001, 61: 4315-9. (Pubitemid 32685750)
102. Locke JA, Guns ES, Lubik AA, et al. Androgen levels increase by intratumoral de novo steroidogenesis during progression of castration-resistant prostate cancer. Cancer Res 2008, 68: 6407-15.
103. Montgomery RB, Mostaghel EA, Vessella R, et al. Maintenance of intratumoral androgens in metastatic prostate cancer: a mechanism for castration-resistant tumor growth. Cancer Res 2008, 68: 4447-54.
104. Hofland J, van Weerden WM, Dits NF, et al. Evidence of limited contributions for intratumoral steroidogenesis in prostate cancer. Cancer Res 2010, 70: 1256-64.
105. Tomlins SA, Rhodes DR, Perner S, et al. Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science 2005, 310: 644-8.
106. Mackinnon AC, Yan BC, Joseph LJ, Al-Ahmadie HA. Molecular biology underlying the clinical heterogeneity of prostate cancer: an update. Arch Pathol Lab Med 2009, 133: 1033-40.
107. Baldi E, Bonaccorsi L, Nesi G, Serni S, Forti G, Luzzatto L. TMPRSS2:ERG fusion gene and androgen-ablation therapy in prostate cancer. Arch Pathol Lab Med 2010, 134: 964-5.
108. Baldi E, Bonaccorsi L, Forti G. Androgen receptor: good guy or bad guy in prostate cancer invasion? Endocrinology 2003, 144: 1653-5.
109. Niu Y, Chang TM, Yeh S, Ma WL, Wang YZ, Chang C. Differential androgen receptor signals in different cells explain why androgendeprivation therapy of prostate cancer fails. Oncogene 2010, 29: 3593-604.
110. Sarker D, Reid AH, Yap TA, de Bono JS. Targeting the PI3K/AKT pathway for the treatment of prostate cancer. Clin Cancer Res 2009, 15: 4799-805.
111. Signoretti S, Montironi R, Manola J, et al. Her-2-neu expression and progression toward androgen independence in human prostate cancer. J Natl Cancer Inst 2000, 92: 1918-25. (Pubitemid 32036922)
112. Culig Z. Androgen receptor cross-talk with cell signalling pathways. Growth Factors 2004, 22: 179-84. (Pubitemid 39377910)
113. Alimonti A, Nardella C, Chen Z, et al. A novel type of cellular senescence that can be enhanced in mouse models and human tumor xenografts to suppress prostate tumorigenesis. J Clin Invest 2010, 120: 681-93.
114. Vashchenko N, Abrahamsson PA. Neuroendocrine differentiation in prostate cancer: implications for new treatment modalities. Eur Urol 2005, 47: 147-55. (Pubitemid 40126970)
115. Theodorescu D, Broder SR, Boyd JC, Mills SE, Frierson HF Jr. Cathepsin D and chromogranin A as predictors of long term disease specific survival after radical prostatectomy for localized carcinoma of the prostate. Cancer 1997, 80: 2109-19. (Pubitemid 27506024)
116. Weinstein MH, Partin AW, Veltri RW, Epstein JI. Neuroendocrine differentiation in prostate cancer: enhanced prediction of progression after radical prostatectomy. Hum Pathol 1996, 27: 683-7. (Pubitemid 26240320)
117. Jin RJ, Wang Y, Masumori N, et al. NE-10 neuroendocrine cancer promotes the LNCaP xenograft growth in castrated mice. Cancer Res 2004, 64: 5489-95. (Pubitemid 39006573)
118. Amorino GP, Parsons SJ. Neuroendocrine cells in prostate cancer. Crit Rev Eukaryot Gene Expr 2004, 14: 287-300. (Pubitemid 40221058)
119. Marchiani S, Tamburrino L, Nesi G, et al. Androgen-responsive and -unresponsive prostate cancer cell lines respond differently to stimuli inducing neuroendocrine differentiation. Int J Androl 2010, 33: 784-93.
120. Niu Y, Altuwaijri S, Lai KP, et al. Androgen receptor is a tumor suppressor and proliferator in prostate cancer. Proc Natl Acad Sci USA 2008, 105: 12182-7.
121. Niu Y, Altuwaijri S, Yeh S, et al. Targeting the stromal androgen receptor in primary prostate tumors at earlier stages. Proc Natl Acad Sci USA 2008, 105: 12188-93.
122. Bonaccorsi L, Carloni V, Muratori M, et al. Androgen receptor expression in prostate carcinoma cells suppresses alpha6beta4 integrin-mediated invasive phenotype. Endocrinology 2000, 141: 3172-82.
123. Bonaccorsi L, Carloni V, Muratori M, Formigli, et al. EGF receptor (EGFR) signaling promoting invasion is disrupted in androgen-sensitive prostate cancer cells by an interaction between EGFR and androgen receptor (AR). Int J Cancer 2004, 112: 78-86. (Pubitemid 39249494)
124. Bonaccorsi L, Nosi D, Muratori M, Formigli L, Forti G, Baldi E. Altered endocytosis of epidermal growth factor receptor in androgen receptor positive prostate cancer cell lines. J Mol Endocrinol 2007, 38: 51-66. (Pubitemid 46351592)
125. Cinar B, Koeneman KS, Edlund M, Prins GS, Zhau HE, Chung LW. Androgen receptor mediates the reduced tumor growth, enhanced androgen responsiveness, and selected target gene transactivation in a human prostate cancer cell line. Cancer Res 2001, 61: 7310-7. (Pubitemid 32946530)
126. Davis R, Jia D, Cinar B, et al. Functional androgen receptor confers sensitization of androgen-independent prostate cancer cells to anticancer therapy via caspase activation. Biochem Biophys Res Commun 2003, 309: 937-45. (Pubitemid 37122620)
127. Guerini V, Sau D, Scaccianoce E, et al. The androgen derivative 5alpha-androstane-3beta, 17beta-diol inhibits prostate cancer cell migration through activation of the estrogen receptor beta subtype. Cancer Res 2005, 65: 5445-53. (Pubitemid 40827358)
128. Nightingale J, Chaudhary KS, Abel PD, et al. Ligand activation of the androgen receptor downregulates E-cadherin-mediated cell adhesion and promotes apoptosis of prostatic cancer cells. Neoplasia 2003, 5: 347-61. (Pubitemid 37048612)
129. Berger R, Febbo PG, Majumder PK, et al. Androgen-induced differentiation and tumorigenicity of human prostate epithelial cells. Cancer Res 2004, 64: 8867-75. (Pubitemid 39665491)
130. Zhu ML, Kyprianou N. Role of androgens and the androgen receptor in epithelial-mesenchymal transition and invasion of prostate cancer cells. FASEB J 2010, 24: 769-77.
131. Kleeberger W, Bova GS, Nielsen ME, et al. Roles for the stem cell associated intermediate filament Nestin in prostate cancer migration and metastasis. Cancer Res 2007, 67: 9199-206. (Pubitemid 47535906)
132. Debes JD, Tindall DJ. Mechanisms of androgen-refractory prostate cancer. N Engl J Med 2004, 351: 1488-90.