Effects of androgen and estrogen receptor signaling pathways on bladder cancer initiation and progression

Bladder Cancer

Volumn 2, Issue 2, 2016, Pages 127-137

  Godoy, Guilherme ^a   Gakis, Georgios ^b   Smith, Carolyn L ^a   Fahmy, Omar ^b  

^a BAYLOR COLLEGE OF MEDICINE   (United States)

^b UNIVERSITY OF TÜBINGEN   (Germany)

Author keywords

Androgen; Androgen antagonists; Androgens; Carcinogenesis; Disease progression; Estrogen; Estrogen receptor modulators; Estrogens; Receptor; Receptors; Urinary bladder neoplasms

Indexed keywords

EID: 85009163795     PISSN: 23523727     EISSN: 23523735     Source Type: Journal    
DOI: 10.3233/BLC-160052     Document Type: Review

References (77)

1. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin 2015;65(2):87-108.
2. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin 2016;66(1):7-30.
3. Burger M, Catto JW, Dalbagni G, Grossman HB, Herr H, Karakiewicz P, Kassouf W, Kiemeney LA, La Vecchia C, Shariat S, Lotan Y. Epidemiology and risk factors of urothelial bladder cancer. Eur Urol 2013;63(2):234-41.
4. Babjuk M, Burger M, Zigeuner R, Shariat SF, van Rhijn BW, Comperat E, Sylvester RJ, Kaasinen E, Bohle A, Palou Redorta J, Roupret M. EAU guidelines on non-muscleinvasive urothelial carcinoma of the bladder: Update 2013. Eur Urol 2013;64(4):639-53.
5. Witjes JA, Comperat E, Cowan NC, De Santis M, Gakis G, Lebret T, Ribal MJ, Van der Heijden AG, Sherif A. EAU guidelines on muscle-invasive and metastatic bladder cancer: Summary of the 2013 guidelines. Eur Urol 2014;65(4):778-92.
6. Malmstrom PU, Sylvester RJ, Crawford DE, Friedrich M, Krege S, Rintala E, Solsona E, Di Stasi SM, Witjes JA. An individual patient data meta-analysis of the long-term outcome of randomised studies comparing intravesical mitomycin C versus bacillus Calmette-Guerin for non-muscle-invasive bladder cancer. Eur Urol 2009;56(2):247-56.
7. Brausi M, Oddens J, Sylvester R, Bono A, van de Beek C, van Andel G, Gontero P, Turkeri L, Marreaud S, Collette S, Oosterlinck W. Side effects of Bacillus Calmette-Guerin (BCG) in the treatment of intermediate-and high-risk Ta, T1 papillary carcinoma of the bladder: Results of the EORTC genito-urinary cancers group randomised phase 3 study comparing one-third dose with full dose and 1 year with 3 years of maintenance BCG. Eur Urol 2014;65(1): 69-76.
8. Jakse G, Hall R, Bono A, Holtl W, Carpentier P, Spaander JP, van der Meijden AP, Sylvester R. Intravesical BCG in patients with carcinoma in situ of the urinary bladder: Longterm results of EORTC GU Group phase II protocol 30861. Eur Urol 2001;40(2):144-50.
9. Bolenz C, Lotan Y, Ashfaq R, Shariat SF. Estrogen and progesterone hormonal receptor expression in urothelial carcinoma of the bladder. Eur Urol 2009;56(6):1093-5.
10. Boorjian S, Ugras S, Mongan NP, Gudas LJ, You X, Tickoo SK, Scherr DS. Androgen receptor expression is inversely correlated with pathologic tumor stage in bladder cancer. Urology 2004;64(2):383-8.
11. Mir C, Shariat SF, van der Kwast TH, Ashfaq R, Lotan Y, Evans A, Skeldon S, Hanna S, Vajpeyi R, Kuk C, Alkhateeb S, Morote J, van Rhijn BW, Bostrom P, Yao J, Miyamoto H, Jewett M, Fleshner N, Messing E, Zlotta AR. Loss of androgen receptor expression is not associated with pathological stage, grade, gender or outcome in bladder cancer: A large multi-institutional study. BJU Int 2011;108(1):24-30.
12. Waliszewski P,Waliszewska MK, Hemstreet GP 3rd, Hurst RE. Expression of sex steroid receptor genes and comodulation with retinoid signaling in normal human uroepithelial cells and bladder cancer cell lines. Urol Oncol 1997;3(5-6):141-7.
13. Castelao JE, Yuan JM, Skipper PL, Tannenbaum SR, Gago-Dominguez M, Crowder JS, Ross RK, Yu MC. Genderand smoking-related bladder cancer risk. J Natl Cancer Inst 2001;93(7):538-45.
14. Hartge P, Harvey EB, Linehan WM, Silverman DT, Sullivan JW, Hoover RN, Fraumeni JF Jr. Unexplained excess risk of bladder cancer in men. J Natl Cancer Inst 1990;82(20): 1636-40.
15. Scelo G, Brennan P. The epidemiology of bladder and kidney cancer. Nat Clin Pract Urol 2007;4(4):205-17.
16. Mungan NA, Aben KK, Schoenberg MP, Visser O, Coebergh JW, Witjes JA, Kiemeney LA. Gender differences in stage-adjusted bladder cancer survival. Urology 2000;55(6):876-80.
17. Najari BB, Rink M, Li PS, Karakiewicz PI, Scherr DS, Shabsigh R, Meryn S, Schlegel PN, Shariat SF. Sex disparities in cancer mortality: The risks of being a man in the United States. J Urol 2013;189(4):1470-4.
18. Vaidya A, Soloway MS, Hawke C, Tiguert R, Civantos F. De novo muscle invasive bladder cancer: Is there a change in trend? J Urol 2001;165(1):47-50; discussion
19. Otto W, May M, Fritsche HM, Dragun D, Aziz A, Gierth M, Trojan L, Herrmann E, Moritz R, Ellinger J, Tilki D, Buchner A, Hofner T, Brookman-May S, Nuhn P, Gilfrich C, Roigas J, Zacharias M, Denzinger S, Hohenfellner M, Haferkamp A, Muller SC, Kocot A, Riedmiller H,Wieland WF, Stief CG, Bastian PJ, Burger M. Analysis of sex differences in cancer-specific survival and perioperative mortality following radical cystectomy: Results of a large German multicenter study of nearly 2500 patients with urothelial carcinoma of the bladder. Gend Med 2012;9(6):481-9.
20. Sammon JD, Morgan M, Djahangirian O, Trinh QD, Sun M, Ghani KR, Jeong W, Jhaveri J, Ehlert M, Schmitges J, Bianchi M, Shariat SF, Perrotte P, Rogers CG, Peabody JO, Menon M, Karakiewicz PI. Marital status: A genderindependent risk factor for poorer survival after radical cystectomy. BJU Int 2012;110(9):1301-9.
21. Shariat SF, Sfakianos JP, Droller MJ, Karakiewicz PI, Meryn S, Bochner BH. The effect of age and gender on bladder cancer: A critical review of the literature. BJU Int 2010; 105(3):300-8.
22. Fernandez-Gomez J, Madero R, Solsona E, Unda M, Martinez-Pineiro L, Gonzalez M, Portillo J, Ojea A, Pertusa C, Rodriguez-Molina J, Camacho JE, Rabadan M, Astobieta A, Montesinos M, Isorna S, Muntanola P, Gimeno A, Blas M, Martinez-Pineiro JA. Predicting nonmuscle invasive bladder cancer recurrence and progression in patients treated with bacillus Calmette-Guerin: The CUETO scoring model. J Urol 2009;182(5):2195-203.
23. Fernandez-Gomez J, Solsona E, Unda M, Martinez-Pineiro L, Gonzalez M, Hernandez R, Madero R, Ojea A, Pertusa C, Rodriguez-Molina J, Camacho JE, Isorna S, Rabadan M, Astobieta A, Montesinos M, Muntanola P, Gimeno A, Blas M, Martinez-Pineiro JA. Prognostic factors in patients with non-muscle-invasive bladder cancer treated with bacillus Calmette-Guerin: Multivariate analysis of data from four randomized CUETO trials. Eur Urol 2008;53(5): 992-1001.
24. Kluth LA, Fajkovic H, Xylinas E, Crivelli JJ, Passoni N, Roupret M, Becker A, Comploj E, Pycha A, Holmang S, Gupta A, Lotan Y, Karakiewicz PI, Gontero P, Chun FK, Fisch M, Scherr DS, Shariat SF. Female gender is associated with higher risk of disease recurrence in patients with primary T1 high-grade urothelial carcinoma of the bladder. World J Urol 2013;31(5):1029-36.
25. Boorjian SA, Zhu F, Herr HW. The effect of gender on response to bacillus Calmette-Guerin therapy for patients with non-muscle-invasive urothelial carcinoma of the bladder. BJU Int 2010;106(3):357-61.
26. Nam JK, Park SW, Lee SD, Chung MK. Prognostic value of sex-hormone receptor expression in non-muscle-invasive bladder cancer. Yonsei Med J 2014;55(5):1214-21.
27. Williams EM, Higgins JP, Sangoi AR, McKenney JK, Troxell ML. Androgen receptor immunohistochemistry in genitourinary neoplasms. Int Urol Nephrol 2015;47(1):81-5.
28. Zhuang YH, Blauer M, Tammela T, Tuohimaa P. Immunodetection of androgen receptor in human urinary bladder cancer. Histopathology 1997;30(6):556-62.
29. Downes MR, Torlakovic EE, Aldaoud N, Zlotta AR, Evans AJ, van der Kwast TH. Diagnostic utility of androgen receptor expression in discriminating poorly differentiated urothelial and prostate carcinoma. J Clin Pathol 2013;66(9):779-86.
30. Mohanty SK, Smith SC, Chang E, Luthringer DJ, Gown AM, Aron M, Amin MB. Evaluation of contemporary prostate and urothelial lineage biomarkers in a consecutive cohort of poorly differentiated bladder neck carcinomas. Am J Clin Pathol 2014;142(2):173-83.
31. Mashhadi R, Pourmand G, Kosari F, Mehrsai A, Salem S, Pourmand MR, Alatab S, Khonsari M, Heydari F, Beladi L, Alizadeh F. Role of steroid hormone receptors in formation and progression of bladder carcinoma:Acase-control study. Urol J 2014;11(6):1968-73.
32. Tuygun C, Kankaya D, Imamoglu A, Sertcelik A, Zengin K, Oktay M, Sertcelik N. Sex-specific hormone receptors in urothelial carcinomas of the human urinary bladder: A comparative analysis of clinicopathological features and survival outcomes according to receptor expression. Urol Oncol 2011;29(1):43-51.
33. Laor E, Schiffman ZJ, Braunstein JD, Reid RE, Tolia BM, Koss LG, Freed SZ. Androgen receptors in bladder tumors. Urology 1985;25(2):161-3.
34. Miyamoto H, Yao JL, Chaux A, Zheng Y, Hsu I, Izumi K, Chang C, Messing EM, Netto GJ, Yeh S. Expression of androgen and oestrogen receptors and its prognostic significance in urothelial neoplasm of the urinary bladder. BJU Int 2012;109(11):1716-26.
35. Boorjian SA, Heemers HV, Frank I, Farmer SA, Schmidt LJ, Sebo TJ, Tindall DJ. Expression and significance of androgen receptor coactivators in urothelial carcinoma of the bladder. Endocr Relat Cancer 2009;16(1):123-37.
36. Kauffman EC, Robinson BD, Downes MJ, Powell LG, Lee MM, Scherr DS, Gudas LJ, Mongan NP. Role of androgen receptor and associated lysine-demethylase coregulators, LSD1 and JMJD2A, in localized and advanced human bladder cancer. Mol Carcinog 2011;50(12):931-44.
37. Comprehensive molecular characterization of urothelial bladder carcinoma. Nature 2014;507(7492):315-22.
38. ChoiW, Porten S, Kim S,Willis D, Plimack ER, Hoffman-Censits J, Roth B, Cheng T, Tran M, Lee IL, Melquist J, Bondaruk J, Majewski T, Zhang S, Pretzsch S, Baggerly K, Siefker-Radtke A, Czerniak B, Dinney CP, McConkey DJ. Identification of distinct basal and luminal subtypes of muscle-invasive bladder cancer with different sensitivities to frontline chemotherapy. Cancer Cell 2014;25(2):152-65.
39. Damrauer JS, Hoadley KA, Chism DD, Fan C, Tiganelli CJ, Wobker SE, Yeh JJ, Milowsky MI, Iyer G, Parker JS, Kim WY. Intrinsic subtypes of high-grade bladder cancer reflect the hallmarks of breast cancer biology. Proc Natl Acad Sci U S A 2014;111(8):3110-5.
40. Heemers HV, Tindall DJ. Androgen receptor (AR) coregulators: A diversity of functions converging on and regulating the AR transcriptional complex. Endocr Rev 2007;28(7):778-808.
41. Luo JH, Xie D, Liu MZ, Chen W, Liu YD, Wu GQ, Kung HF, Zeng YX, Guan XY. Protein expression and amplification of AIB1 in human urothelial carcinoma of the bladder and overexpression of AIB1 is a new independent prognostic marker of patient survival. Int J Cancer 2008;122(11): 2554-61.
42. Tong ZT, Wei JH, Zhang JX, Liang CZ, Liao B, Lu J, Fan S, Chen ZH, Zhang F, Ma HH, Qian WC, Kong LL, Fang Y, Chen W, Xie D, Luo JH. AIB1 predicts bladder cancer outcome and promotes bladder cancer cell proliferation through AKT and E2F1. Br J Cancer 2013;108(7):1470-9.
43. Kihara K, Fukui I, HigashiY, Oshima H. Inhibitory effect of testosterone on gap junctional intercellular communication of human transitional cell carcinoma cell lines. Cancer Res 1990;50(9):2848-52.
44. Wu JT, Han BM, Yu SQ, Wang HP, Xia SJ. Androgen receptor is a potential therapeutic target for bladder cancer. Urology 2010;75(4):820-7.
45. Hsu JW, Hsu I, Xu D, Miyamoto H, Liang L,Wu XR, Shyr CR, Chang C. Decreased tumorigenesis and mortality from bladder cancer in mice lacking urothelial androgen receptor. Am J Pathol 2013;182(5):1811-20.
46. LiY, ZhengY, Izumi K, Ishiguro H,Ye B, Li F, Miyamoto H. Androgen activates beta-catenin signaling in bladder cancer cells. Endocr Relat Cancer 2013;20(3):293-304.
47. Zheng Y, Izumi K, Yao JL, Miyamoto H. Dihydrotestosterone upregulates the expression of epidermal growth factor receptor and ERBB2 in androgen receptor-positive bladder cancer cells. Endocr Relat Cancer 2011;18(4): 451-64.
48. Miyamoto H, Yang Z, Chen YT, Ishiguro H, Uemura H, KubotaY, NagashimaY, Chang YJ, Hu YC, TsaiMY,Yeh S, Messing EM, Chang C. Promotion of bladder cancer development and progression by androgen receptor signals. J Natl Cancer Inst 2007;99(7):558-68.
49. Terada S, Suzuki N, Uchide K, Akasofu K, Nishida E. Effect of testosterone on the development of bladder tumors and calculi in female rats. Gynecol Obstet Invest 1992;34(2):105-10.
50. Okajima E, Hiramatsu T, Iriya K, Ijuin M, Matsushima S. Effects of sex hormones on development of urinary bladder tumours in rats induced by N-butyl-N-(4-hydroxybutyl) nitrosamine. Urol Res 1975;3(2):73-9.
51. Ciotti M, Lakshmi VM, Basu N, Davis BB, Owens IS, Zenser TV. Glucuronidation of benzidine and its metabolites by cDNA-expressed human UDP-glucuronosyl transferases and pH stability of glucuronides. Carcinogenesis 1999;20(10):1963-9.
52. Izumi K, Zheng Y, Hsu JW, Chang C, Miyamoto H. Androgen receptor signals regulate UDP-glucuronosyl transferases in the urinary bladder: A potential mechanism of androgen-induced bladder carcinogenesis. Mol Carcinog 2013;52(2):94-102.
53. Kauffman EC, Robinson BD, Downes M, Marcinkiewicz K, Vourganti S, Scherr DS, Gudas LJ, Mongan NP. Estrogen receptor-beta expression and pharmacological targeting in bladder cancer. Oncol Rep 2013;30(1):131-8.
54. Shen SS, Smith CL, Hsieh JT, Yu J, Kim IY, Jian W, Sonpavde G, Ayala GE, Younes M, Lerner SP. Expression of estrogen receptors-alpha and-beta in bladder cancer cell lines and human bladder tumor tissue. Cancer 2006; 106(12):2610-6.
55. Teng J, Wang ZY, Jarrard DF, Bjorling DE. Roles of estrogen receptor alpha and beta in modulating urothelial cell proliferation. Endocr Relat Cancer 2008;15(1):351-64.
56. Croft PR, Lathrop SL, Feddersen RM, Joste NE. Estrogen receptor expression in papillary urothelial carcinoma of the bladder and ovarian transitional cell carcinoma. Arch Pathol Lab Med 2005;129(2):194-9.
57. Han B, Cui D, Jing Y, Hong Y, Xia S. Estrogen receptor beta (ERbeta) is a novel prognostic marker of recurrence survival in non-muscle-invasive bladder cancer potentially by inhibiting cadherin switch. World J Urol 2012;30(6): 861-7.
58. Kaufmann O, Baume H, Dietel M. Detection of oestrogen receptors in non-invasive and invasive transitional cell carcinomas of the urinary bladder using both conventional immunohistochemistry and the tyramide staining amplification (TSA) technique. J Pathol 1998;186(2): 165-8.
59. Kontos S, Kominea A, Melachrinou M, Balampani E, Sotiropoulou-Bonikou G. Inverse expression of estrogen receptor-beta and nuclear factor-kappaB in urinary bladder carcinogenesis. Int J Urol 2010;17(9):801-9.
60. Tan W, Boorjian S, Advani P, Farmer S, Lohse C, Cheville J, Kwon E, Leibovich B. The estrogen pathway: Estrogen receptor-alpha, progesterone receptor, and estrogen receptor-beta expression in radical cystectomy urothelial cell carcinoma specimens. Clin Genitourin Cancer 2015;13(5):476-84.
61. Wei S, Said-Al-Naief N, Hameed O. Estrogen and progesterone receptor expression is not always specific for mammary and gynecologic carcinomas:Atissue microarray and pooled literature review study. Appl Immunohistochem Mol Morphol 2009;17(5):393-402.
62. Hoffman KL, Lerner SP, Smith CL. Raloxifene inhibits growth of RT4 urothelial carcinoma cells via estrogen receptor-dependent induction of apoptosis and inhibition of proliferation. Horm Cancer 2013;4(1):24-35.
63. Sonpavde G, Okuno N,Weiss H, Yu J, Shen SS, Younes M, JianW, Lerner SP, Smith CL. Efficacy of selective estrogen receptor modulators in nude mice bearing human transitional cell carcinoma. Urology 2007;69(6):1221-6.
64. Izumi K, Li Y, Ishiguro H, Zheng Y, Yao JL, Netto GJ, Miyamoto H. Expression of UDP-glucuronosyltransferase 1A in bladder cancer: Association with prognosis and regulation by estrogen. Mol Carcinog 2014;53(4):314-24.
65. Hsu I, Chuang KL, Slavin S, Da J, Lim WX, Pang ST, O'Brien JH, Yeh S. Suppression of ERbeta signaling via ERbeta knockout or antagonist protects against bladder cancer development. Carcinogenesis 2014;35(3):651-61.
66. Yeh CR, Hsu I, Song W, Chang H, Miyamoto H, Xiao GQ, Li L, Yeh S. Fibroblast ERalpha promotes bladder cancer invasion via increasing the CCL1 and IL-6 signals in the tumor microenvironment. Am J Cancer Res 2015;5(3):1146-57.
67. Hsu I, Yeh CR, Slavin S, Miyamoto H, Netto GJ, Tsai YC, Muyan M, Wu XR, Messing EM, Guancial EA, Yeh S. Estrogen receptor alpha prevents bladder cancer via INPP4B inhibited akt pathway in vitro and in vivo. Oncotarget 2014;5(17):7917-35.
68. Johnson AM, O'Connell MJ, Miyamoto H, Huang J, Yao JL, Messing EM, Reeder JE. Androgenic dependence of exophytic tumor growth in a transgenic mouse model of bladder cancer: A role for thrombospondin-1. BMC Urol 2008;8:7.
69. Zhang ZT, Pak J, Shapiro E, Sun TT, Wu XR. Urotheliumspecific expression of an oncogene in transgenic mice induced the formation of carcinoma in situ and invasive transitional cell carcinoma. Cancer Res 1999;59(14):3512-7.
70. GarciaPV, Apolinario LM, Bockelmann PK, da Silva Nunes I, Duran N, Favaro WJ. Alterations in ubiquitin ligase Siah-2 and its corepressor N-CoR after P-MAPA immunotherapy and anti-androgen therapy: New therapeutic opportunities for non-muscle invasive bladder cancer. Int J Clin Exp Pathol 2015;8(5):4427-43.
71. Shang Z, LiY, Zhang M,Tian J, Han R, Shyr CR, Messing E, Yeh S, Niu Y, Chang C. Antiandrogen therapy with hydroxyflutamide or androgen receptor degradation enhancer ASC-J9 enhances BCG efficacy to better suppress bladder cancer progression. Mol Cancer Ther 2015;14(11):2586-94.
72. Pu YS, Hsieh TS, Tsai TC, Cheng AL, Hsieh CY, Su IJ, Lai MK. Tamoxifen enhances the chemosensitivity of bladder carcinoma cells. J Urol 1995;154(2 Pt 1):601-5.
73. Pu YS, Hsieh TS, Cheng AL, Tseng NF, Su IJ, Hsieh CY, Lai MK, Tsai TC. Combined cytotoxic effects of tamoxifen and chemotherapeutic agents on bladder cancer cells: A potential use in intravesical chemotherapy. Br J Urol 1996;77(1):76-85.
74. George SK, Tovar-Sepulveda V, Shen SS, Jian W, Zhang Y, Hilsenbeck SG, Lerner SP, Smith CL. Chemoprevention of BBN-induced bladder carcinogenesis by the selective estrogen receptor modulator tamoxifen. Transl Oncol 2013;6(3):244-55.
75. Izumi K, Taguri M, Miyamoto H, Hara Y, Kishida T, Chiba K, Murai T, Hirai K, Suzuki K, Fujinami K, Ueki T, Udagawa K, Kitami K, Moriyama M, Miyoshi Y, Tsuchiya F, Ikeda I, Kobayashi K, Sato M, Morita S, Noguchi K, Uemura H. Androgen deprivation therapy prevents bladder cancer recurrence. Oncotarget 2014;5(24):12665-74.
76. Dellagrammaticas D, Bryden AA, Collins GN. Regression of metastatic transitional cell carcinoma in response to tamoxifen. J Urol 2001;165(5):1631.
77. Hsu CH, Chen J, Wu CY, Cheng AL, Pu YS. Combination chemotherapy of cisplatin, methotrexate, vinblastine, and high-dose tamoxifen for transitional cell carcinoma. Anticancer Res 2001;21(1B):711-5.