In touch with your feminine side: how oestrogen metabolism impacts prostate cancer

in Endocrine-Related Cancer
Authors:
Habibur P Rahman Institute of Metabolism and Systems Research, University of Birmingham, Birmingham

Search for other papers by Habibur P Rahman in
Current site
Google Scholar
PubMed
Close
,
Johannes Hofland Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands

Search for other papers by Johannes Hofland in
Current site
Google Scholar
PubMed
Close
, and
Paul A Foster Institute of Metabolism and Systems Research, University of Birmingham, Birmingham
Centre for Endocrinology, Diabetes and Metabolism, Birmingham Healthcare Partners, Birmingham, UK

Search for other papers by Paul A Foster in
Current site
Google Scholar
PubMed
Close

Restricted access
Rent on DeepDyve

Sign up for journal news

Prostate cancer is the primary cancer in males, with increasing global incidence rates making this malignancy a significant healthcare burden. Androgens not only promote normal prostate maturity but also influence the development and progression of prostate cancer. Intriguingly, evidence now suggests endogenous and exogenous oestrogens, in the form of phytoestrogens, may be equally as relevant as androgens in prostate cancer growth. The prostate gland has the molecular mechanisms, catalysed by steroid sulphatase (STS), to unconjugate and utilise circulating oestrogens. Furthermore, prostate tissue also expresses enzymes essential for local oestrogen metabolism, including aromatase (CYP19A1) and 3β- and 17β-hydroxysteroid dehydrogenases. Increased expression of these enzymes in malignant prostate tissue compared with normal prostate indicates that oestrogen synthesis is favoured in malignancy and thus may influence tumour progression. In contrast to previous reviews, here we comprehensively explore the epidemiological and scientific evidence on how oestrogens impact prostate cancer, particularly focusing on pre-receptor oestrogen metabolism and subsequent molecular action. We analyse how molecular mechanisms and metabolic pathways involved in androgen and oestrogen synthesis intertwine to alter prostate tissue. Furthermore, we speculate on whether oestrogen receptor status in the prostate affects progression of this malignancy.

 

  • Collapse
  • Expand
  • Acconcia F, Totta P, Ogawa S, Cardillo I, Inoue S, Leone S, Trentalance A, Muramatsu M & Marino M 2005 Survival versus apoptotic 17β-estradiol effect: role of ERα and ERβ activated non-genomic signaling. Journal of Cellular Physiology 203 193201. (doi:10.1002/jcp.20219)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Adams KF, Chen C, Newton KM, Potter JD & Lampe JW 2004 Soy isoflavones do not modulate prostate-specific antigen concentrations in older men in a randomized controlled trial. Cancer Epidemiology Biomarkers & Prevention 13 644648.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Adeniji AO, Chen M & Penning TM 2013 AKR1C3 as a target in castrate resistant prostate cancer. Journal of Steroid Biochemistry and Molecular Biology 137 136149. (doi:10.1016/j.jsbmb.2013.05.012)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Adlercreutz H, Mazur W, Bartels P, Elomaa V-V, Watanabe S, Wähälä K, Landström M, Lundin E, Bergh A, Damber J-E, et al.2000 Phytoestrogens and prostate disease. Journal of Nutrition 130 658.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Allen NE, Appleby PN, Davey GK & Key TJ 2002 Lifestyle and nutritional determinants of bioavailable androgens and related hormones in British men. Cancer Causes & Control 13 353363.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Allott EH, Masko EM & Freedland SJ 2013 Obesity and prostate cancer: weighing the evidence. European Urology 63 800809. (doi:10.1016/j.eururo.2012.11.013)

  • Barazani Y, Katz BF, Nagler HM & Stember DS 2014 Lifestyle, environment, and male reproductive health. Urologic Clinics of North America 41 5566. (doi:10.1016/j.ucl.2013.08.017)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Barzi A, Lenz AM, Labonte MJ & Lenz H-J 2013 Molecular pathways: estrogen pathway in colorectal cancer. Clinical Cancer Research 19 58425848. (doi:10.1158/1078-0432.CCR-1113-0325)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Beer TM, Armstrong AJ, Rathkopf DE, Loriot Y, Sternberg CN, Higano CS, Iversen P, Bhattacharya S, Carles J, Chowdhury S, et al.2014 Enzalutamide in metastatic prostate cancer before chemotherapy. New England Journal of Medicine 371 424433. (doi:10.1056/NEJMoa1405095)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Bhatt S, Xiao Z, Meng Z & Katzenellenbogen BS 2012 Phosphorylation by p38 mitogen-activated protein kinase promotes estrogen receptorαturnover and functional activity via the SCF(Skp2) proteasomal complex. Molecular and Cellular Biology 32 19281943. (doi:10.1128/MCB.06561-11)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Block JL, Block NL & Lokeshwar BL 1996 Modulation of aromatase activity by growth factors in an androgen sensitive human prostate cancer cell line, LNCaP. Cancer Letters 102 167172. (doi:10.1016/0304-3835(96)04176-6)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Bosset P-O, Albiges L, Seisen T, de la Motte Rouge T, Phé V, Bitker M-O & Rouprêt M 2012 Current role of diethylstilbestrol in the management of advanced prostate cancer. BJU International 110 E826E829. (doi:10.1111/j.1464-410X.2012.11206.x)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Brooke GN & Bevan CL 2009 The role of androgen receptor mutations in prostate cancer progression. Current Genomics 10 1825. (doi:10.2174/138920209787581307)

  • Bulun SE, Economos K, Miller D & Simpson ER 1994 CYP19 (aromatase cytochrome P450) gene expression in human malignant endometrial tumors. Journal of Clinical Endocrinology & Metabolism 79 18311834. (doi:10.1210/jcem.79.6.7989490)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Burns KA & Korach KS 2012 Estrogen receptors and human disease: an update. Archives of Toxicology 86 14911504. (doi:10.1007/s00204-012-0868-5)

  • Buxhofer-Ausch V, Secky L, Wlcek K, Svoboda M, Kounnis V, Briasoulis E, Tzakos AG, Jaeger W & Thalhammer T 2013 Tumor-specific expression of organic anion-transporting polypeptides: transporters as novel targets for cancer therapy. Journal of Drug Delivery 2013 863539. (doi:10.1155/2013/863539)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Capper CP, Larios JM, Sikora MJ, Johnson MD & Rae JM 2016 The CYP17A1 inhibitor abiraterone exhibits estrogen receptor agonist activity in breast cancer. Breast Cancer Research and Treatment 18. (doi:10.1007/s10549-016-3774-3)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Center MM, Jemal A, Lortet-Tieulent J, Ward E, Ferlay J, Brawley O & Bray F 2012 International variation in prostate cancer incidence and mortality rates. European Urology 61 10791092. (doi:10.1016/j.eururo.2012.02.054)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Chan QK, Lam H-M, Ng C-F, Lee AY, Chan ES, Ng H-K, Ho S-M & Lau K-M 2010 Activation of GPR30 inhibits the growth of prostate cancer cells through sustained activation of Erk1/2, c-jun/c-fos-dependent upregulation of p21, and induction of G2 cell-cycle arrest. Cell Death & Differentiation 17 15111523. (doi:10.1038/cdd.2010.20)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Chang K-H, Li R, Papari-Zareei M, Watumull L, Zhao YD, Auchus RJ & Sharifi N 2011 Dihydrotestosterone synthesis bypasses testosterone to drive castration-resistant prostate cancer. PNAS 108 1372813733. (doi:10.1073/pnas.1107898108)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Chen S 1998 Aromatase and breast cancer. Frontiers in Bioscience: A Journal and Virtual Library 3 d922d933.

  • Chen CD, Welsbie DS, Tran C, Baek SH, Chen R, Vessella R, Rosenfeld MG & Sawyers CL 2004 Molecular determinants of resistance to antiandrogen therapy. Nature Medicine 10 3339. (doi:10.1038/nm972)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Chen M, Ni J, Chang H-C, Lin C-Y, Muyan M & Yeh S 2009 CCDC62/ERAP75 functions as a coactivator to enhance estrogen receptor beta-mediated transactivation and target gene expression in prostate cancer cells. Carcinogenesis 30 841850. (doi:10.1093/carcin/bgn288)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Chen M, Yeh C-R, Chang H-C, Vitkus S, Wen X-Q, Bhowmick NA, Wolfe A & Yeh S 2012 Loss of epithelial oestrogen receptorαinhibits oestrogen-stimulated prostate proliferation and squamous metaplasia via in vivo tissue selective knockout models. Journal of Pathology 226 1727. (doi:10.1002/path.2949)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Chevalier N, Bouskine A & Fenichel P 2011 Role of GPER/GPR30 in tumoral testicular germ cells proliferation. Cancer Biology & Therapy 12 23. (doi:10.4161/cbt.12.1.15726)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Christoforou P, Christopoulos PF & Koutsilieris M 2014 The role of estrogen receptor β in prostate cancer. Molecular Medicine 20 427434. (doi:10.2119/molmed.2014.00105)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Claessens F, Helsen C, Prekovic S, Van den Broeck T, Spans L, Van Poppel H & Joniau S 2014 Emerging mechanisms of enzalutamide resistance in prostate cancer. Nature Reviews. Urology 11 712716. (doi:10.1038/nrurol.2014.243)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Clemons J, Glodé LM, Gao D & Flaig TW 2013 Low-dose diethylstilbestrol for the treatment of advanced prostate cancer. Urologic Oncology: Seminars and Original Investigations 31 198204. (doi:10.1016/j.urolonc.2010.12.004)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Cook LS, Goldoft M, Schwartz SM & Weiss NS 1999 Incidence of adenocarcinoma of the prostate in asian immigrants to the United States and their descendants. Journal of Urology 161 152155. (doi:10.1016/S0022-5347(01)62086-X)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Cui J, Shen Y & Li R 2013 Estrogen synthesis and signaling pathways during ageing: from periphery to brain. Trends in Molecular Medicine 19 197209. (doi:10.1016/j.molmed.2012.12.007)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Cunha GR 1994 Role of mesenchymal-epithelial interactions in normal and abnormal development of the mammary gland and prostate. Cancer 74 10301044. (doi:10.1002/1097-0142(19940801)74:3+<1030::aid-cncr2820741510>3.0.co;2-q)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Da J, Lu M & Wang Z 2015 Estrogen receptor alpha (ERα)-associated fibroblasts promote cell growth in prostate cancer. Cell Biochemistry and Biophysics 73 793798. (doi:10.1007/s12013-015-0700-y)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Daniels NA, Nielson CM, Hoffman AR & Bauer DC 2010 Sex hormones and the risk of incident prostate cancer. Urology 76 10341040. (doi:10.1016/j.urology.2010.01.086)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Davies JH, Dowsett M, Jacobs S, Coombes RC, Hedley A & Shearer RJ 1992 Aromatase inhibition: 4-hydroxyandrostenedione (4-OHA, CGP 32349) in advanced prostatic cancer. British Journal of Cancer 66 139142. (doi:10.1038/bjc.1992.231)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Day JM, Foster PA, Tutill HJ, Schmidlin F, Sharland CM, Hargrave JD, Vicker N, Potter BVL, Reed MJ & Purohit A 2013 STX2171, a 17β-hydroxysteroid dehydrogenase type 3 inhibitor, is efficacious in vivo in a novel hormone-dependent prostate cancer model. Endocrine-Related Cancer 20 5364. (doi:10.1530/ERC-12-0231)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • de Bono JS, Logothetis CJ, Molina A, Fizazi K, North S, Chu L, Chi KN, Jones RJ, Goodman OBJ, Saad F, et al.2011 Abiraterone and increased survival in metastatic prostate cancer. New England Journal of Medicine 364 19952005. (doi:10.1056/NEJMoa1014618)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • De Nunzio C, Albisinni S, Freedland SJ, Miano L, Cindolo L, Finazzi Agrò E, Autorino R, De Sio M, Schips L & Tubaro A 2013 Abdominal obesity as risk factor for prostate cancer diagnosis and high grade disease: a prospective multicenter Italian cohort study. Urologic Oncology: Seminars and Original Investigations 31 9971002. (doi:10.1016/j.urolonc.2011.08.007)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Deblois G & Giguere V 2013 Oestrogen-related receptors in breast cancer: control of cellular metabolism and beyond. Nature Reviews. Cancer 13 2736. (doi:10.1038/nrc3396)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • deVere White RW, Hackman RM, Soares SE, Beckett LA, Li Y & Sun B 2004 Effects of a genistein-rich extract on PSA levels in men with a history of prostate cancer. Urology 63 259263. (doi:10.1016/j.urology.2003.09.061)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Dey P, Strom A & Gustafsson JA 2014 Estrogen receptor [beta] upregulates FOXO3a and causes induction of apoptosis through PUMA in prostate cancer. Oncogene 33 42134225. (doi:10.1038/onc.2013.384)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Di Zazzo E, Galasso G, Giovannelli P, Di Donato M, Di Santi A, Cernera G, Rossi V, Abbondanza C, Moncharmont B, Sinisi AA, et al.2016 Prostate cancer stem cells: the role of androgen and estrogen receptors. Oncotarget 7 193208. (doi:10.18632/oncotarget.6220)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Ellem SJ & Risbridger GP 2007 Treating prostate cancer: a rationale for targeting local oestrogens. Nature Reviews. Cancer 7 621627. (doi:10.1038/nrc2174)

  • Ellem SJ & Risbridger GP 2009 The dual, opposing roles of estrogen in the prostate. Annals of the New York Academy of Sciences 1155 174186. (doi:10.1111/j.1749-6632.2009.04360.x)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Ellem SJ & Risbridger GP 2010 Aromatase and regulating the estrogen: androgenratio in the prostate gland. Journal of Steroid Biochemistry and Molecular Biology 118 246251. (doi:10.1016/j.jsbmb.2009.10.015)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Ellem SJ, Schmitt JF, Pedersen JS, Frydenberg M & Risbridger GP 2004 Local aromatase expression in human prostate is altered in malignancy. Journal of Clinical Endocrinology & Metabolism 89 24342441. (doi:10.1210/jc.2003-030933)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Evaul K, Li R, Papari-Zareei M, Auchus RJ & Sharifi N 2010 3β-Hydroxysteroid dehydrogenase is a possible pharmacological target in the treatment of castration-resistant prostate cancer. Endocrinology 151 35143520. (doi:10.1210/en.2010-0138)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Farnsworth WE 1973 Human prostatic dehydroepiandrosterone sulfate sulfatase. Steroids 21 647664. (doi:10.1016/0039-128X(73)90134-7)

  • Foster PA 2013 Oestrogen and colorectal cancer: mechanisms and controversies. International Journal of Colorectal Disease 28 737749. (doi:10.1007/s00384-012-1628-y)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Foster PA, Newman SP, Chander SK, Stengel C, Jhalli R, Woo LL, Potter BV, Reed MJ & Purohit A 2006 In vivo efficacy of STX213, a second-gegneration steroid sulfatase inhibitor, for hormone-dependent breast cancer therapy. Clinical Cancer Research 12 55435549. (doi:10.1158/1078-0432.CCR-06-0632)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Foster PA, Chander SK, Parsons MF, Newman SP, Woo LW, Potter BV, Reed MJ & Purohit A 2008 Efficacy of three potent steroid sulfatase inhibitors: pre-clinical investigations for their use in the treatment of hormone-dependent breast cancer. Breast Cancer Research and Treatment 111 12938. (doi:10.1007/s10549-007-9769-3)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Francis JC, Thomsen MK, Taketo MM & Swain A 2013 β-catenin is required for prostate development and cooperates with Pten loss to drive invasive carcinoma. PLoS Genetics 9 e1003180.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Fu C, Dong W-Q, Wang A & Qiu G 2014 The influence of ESR1 rs9340799 and ESR2 rs1256049 polymorphisms on prostate cancer risk. Tumor Biology 35 83198328. (doi:10.1007/s13277-014-2086-7)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Gautier A, Bonnet F, Dubois S, Massart C, Grosheny C, Bachelot A, Aubé C, Balkau B & Ducluzeau P-H 2013 Associations between visceral adipose tissue, inflammation and sex steroid concentrations in men. Clinical Endocrinology 78 373378. (doi:10.1111/j.1365-2265.2012.04401.x)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Geier R, Adler S, Rashid G & Klein A 2010 The synthetic estrogen diethylstilbestrol (DES) inhibits the telomerase activity and gene expression of prostate cancer cells. Prostate 70 13071312. (doi:10.1002/pros.21166)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Giton F, Sirab N, Franck G, Gervais M, Schmidlin F, Ali T, Allory Y, Taille Adl, Vacherot F, Loric S, et al.2015 Evidence of estrone-sulfate uptake modification in young and middle-aged rat prostate. Journal of Steroid Biochemistry and Molecular Biology 152 89100. (doi:10.1016/j.jsbmb.2015.05.002)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Goetzl MA, VanVeldhuizen PJ & Thrasher JB 2007 Effects of soy phytoestrogens on the prostate. Prostate Cancer and Prostatic Diseases 10 216223. (doi:10.1038/sj.pcan.4500953)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Gooren L & Morgentaler A 2014 Prostate cancer incidence in orchidectomised male-to-female transsexual persons treated with oestrogens. Andrologia 46 11561160. (doi:10.1111/and.12208)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Grönberg H 2003 Prostate cancer epidemiology. Lancet 361 859864. (doi:10.1016/S0140-6736(03)12713-4)

  • Hanahan D & Weinberg Robert A 2011 Hallmarks of cancer: the next generation. Cell 144 646674. (doi:10.1016/j.cell.2011.02.013)

  • Hariri W, Sudha T, Bharali DJ, Cui H & Mousa SA 2015 Nano-targeted delivery of toremifene, an estrogen receptor-α blocker in prostate cancer. Pharmaceutical Research 32 27642774.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Härkönen PL & Mäkelä SI 2004 Role of estrogens in development of prostate cancer. Journal of Steroid Biochemistry and Molecular Biology 92 297305. (doi:10.1016/j.jsbmb.2004.10.016)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Henderson BE, Bernstein L, Ross RK, Depue RH & Judd HL 1988 The early in utero oestrogen and testosterone environment of blacks and whites: potential effects on male offspring. British Journal of Cancer 57 216218. (doi:10.1038/bjc.1988.46)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Ho S-M 2004 Estrogens and anti-estrogens: key mediators of prostate carcinogenesis and new therapeutic candidates. Journal of Cellular Biochemistry 91 491503. (doi:10.1002/jcb.10759)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Hofland J, van Weerden WM, Dits NFJ, Steenbergen J, van Leenders GJLH, Jenster G, Schröder FH & de Jong FH 2010 Evidence of limited contributions for intratumoral steroidogenesis in prostate cancer. Cancer Research 70 12561264. (doi:10.1158/0008-5472.CAN-09-2092)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Hofland J, Weerden WMv, Steenbergen J, Dits NFJ, Jenster G & Jong FHd 2011 Activin A regulates local testosterone production and growth in prostate cancer through 17β-hydroxysteroid dehydrogenase. In 13th European Congress of Endocrinology, p 353. Rotterdam, The Netherlands: Endocrine Abstracts, Bioscientifica.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Holt SK, Kwon EM, Fu R, Kolb S, Feng Z, Ostrander EA & Stanford JL 2013 Association of variants in estrogen-related pathway genes with prostate cancer risk. Prostate 73 110. (doi:10.1002/pros.22534)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Howell MA 1974 Factor analysis of international cancer mortality data and per capita food consumption. British Journal of Cancer 29 328336. (doi:10.1038/bjc.1974.75)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Huang W, Chen Y, Liu Y, Zhang Q, Yu Z, Mou L, Wu H, Zhao L, Long T, Qin D, et al.2015 Roles of ERβ and GPR30 in proliferative response of human bladder cancer cell to estrogen. BioMed Research International 2015 251780.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Huggins C & Hodges CV 1941 Studies on prostatic cancer. I. The effect of castration, of estrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate. Cancer Research 1 293297.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Hussain S, Lawrence MG, Taylor RA, Lo CY-W, BioResource APC, Frydenberg M, Ellem SJ, Furic L & Risbridger GP 2012 Estrogen receptorβactivation impairs prostatic regeneration by inducing apoptosis in murine and human stem/progenitor enriched cell populations. PLoS ONE 7 e40732.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Jacob M & Henrik M 2006 One, five and ten year cancer prevalence by Cancer Network, UK, 2006. In One, Five and Ten Year Cancer Prevalence by Cancer Network, UK. London, UK: National Cancer Intelligence Network.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Jasuja GK, Travison TG, Davda M, Murabito JM, Basaria S, Zhang A, Kushnir MM, Rockwood AL, Meikle W, Pencina MJ, et al.2013 Age trends in estradiol and estrone levels measured using liquid chromatography tandem mass spectrometry in community-dwelling men of the framingham heart study. Journals of Gerontology Series A: Biological Sciences and Medical Sciences 68 733740. (doi:10.1093/gerona/gls216)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Jurečeková J, Babušíková E, Kmeťová M, Kliment J & Dobrota D 2015 Estrogen receptor alpha polymorphisms and the risk of prostate cancer development. Journal of Cancer Research and Clinical Oncology 141 19631971. (doi:10.1007/s00432-015-1966-6)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Khurana I 2008 Essentials of Medical Physiology. New Delhi, India: Elsevier India Pvt. Limited.

  • Kimbro K & Simons J 2006 Hypoxia-inducible factor-1 in human breast and prostate cancer. Endocrine-Related Cancer 13 739749. (doi:10.1677/erc.1.00728)

  • King KJ, Nicholson HD & Assinder SJ 2006 Effect of increasing ratio of estrogen: androgen on proliferation of normal human prostate stromal and epithelial cells, and the malignant cell line LNCaP. Prostate 66 105114. (doi:10.1002/pros.20327)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Klein H, Molwitz T & Bartsch W 1989 Steroid sulfate sulfatase in human benign prostatic hyperplasia: characterization and quantification of the enzyme in epithelium and stroma. Journal of Steroid Biochemistry 33 195200. (doi:10.1016/0022-4731(89)90294-X)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Knochenhauer ES, Boots LR, Potter HD & Azziz R 1998 Differential binding of estradiol and testosterone to SHBG. Relation to circulating estradiol levels. Journal of Reproductive Medicine 43 665670.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Koh E, Noda T, Kanaya J & Namiki M 2002 Differential expression of 17β2010hydroxysteroid dehydrogenase isozyme genes in prostate cancer and noncancer tissues. Prostate 53 154159. (doi:10.1002/pros.10139)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Kolonel LN, Altshuler D & Henderson BE 2004 The multiethnic cohort study: exploring genes, lifestyle and cancer risk. Nature Reviews. Cancer 4 519527. (doi:10.1038/nrc1389)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Kuiper GGJM, Lemmen JG, Carlsson B, Corton JC, Safe SH, Saag PTvd, Burg Bvd & Gustafsson J-Å 1998 Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor β. Endocrinology 139 42524263. (doi:10.1210/endo.139.10.6216)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Kumagai J, Hofland J, Erkens-Schulze S, Dits NFJ, Steenbergen J, Jenster G, Homma Y, de Jong FH & van Weerden WM 2013 Intratumoral conversion of adrenal androgen precursors drives androgen receptor-activated cell growth in prostate cancer more potently than de novo steroidogenesis. Prostate 73 16361650. (doi:10.1002/pros.22655)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Labrie F, Bélanger A, Luu-The V, Labrie C, Simard J, Cusan L, Gomez J & Candas B 2005 Gonadotropin-releasing hormone agonists in the treatment of prostate cancer. Endocrine Reviews 26 361379. (doi:10.1210/er.2004-0017)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Lam H-M, Ouyang B, Chen J, Ying J, Wang J, Wu C-L, Jia L, Medvedovic M, Vessella RL & Ho S-M 2014 Targeting GPR30 with G-1: a new therapeutic target for castration-resistant prostate cancer. Endocrine-Related Cancer 21 903914. (doi:10.1530/ERC-14-0402)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Lee J, Demissie K, Lu S & Rhoads GG 2007 Cancer incidence among Korean-American immigrants in the United States and native Koreans in South Korea. Cancer Control 14 78.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Leung Y-K, Mak P, Hassan S & Ho S-M 2006 Estrogen receptor (ER)-β isoforms: a key to understanding ER-β signaling. PNAS 103 1316213167. (doi:10.1073/pnas.0605676103)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Leung Y-K, Lam H-M, Wu S, Song D, Levin L, Cheng L, Wu C-L & Ho S-M 2010 Estrogen receptor β2 and β5 are associated with poor prognosis in prostate cancer, and promote cancer cell migration and invasion. Endocrine-Related Cancer 17 675689. (doi:10.1677/ERC-09-0294)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Li R, Evaul K, Sharma KK, Chang K-H, Yoshimoto J, Liu J, Auchus RJ & Sharifi N 2012 Abiraterone inhibits 3β-hydroxysteroid dehydrogenase: a rationale for increasing drug exposure in castration-resistant prostate cancer. Clinical Cancer Research 18 35713579. (doi:10.1158/1078-0432.CCR-12-0908)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Li Y, Wu Y, Abbatiello TC, Wu WL, Kim JR, Sarkissyan M, Sarkissyan S, Chung SS, Elshimali Y & Vadgama JV 2015a Slug contributes to cancer progression by direct regulation of ERα signaling pathway. International Journal of Oncology 46 14611472.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Li Z, Bishop AC, Alyamani M, Garcia JA, Dreicer R, Bunch D, Liu J, Upadhyay SK, Auchus RJ & Sharifi N 2015b Conversion of abiraterone to D4A drives anti-tumour activity in prostate cancer. Nature 523 347351. (doi:10.1038/nature14406)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Liu C, Lou W, Zhu Y, Yang JC, Nadiminty N, Gaikwad NW, Evans CP & Gao AC 2015 Intracrine androgens and AKR1C3 activation confer resistance to enzalutamide in prostate cancer. Cancer Research 75 14131422. (doi:10.1158/0008-5472.CAN-14-3080)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Locke JA, Guns ES, Lubik AA, Adomat HH, Hendy SC, Wood CA, Ettinger SL, Gleave ME & Nelson CC 2008 Androgen levels increase by intratumoral de novo steroidogenesis during progression of castration-resistant prostate cancer. Cancer Research 68 64076415. (doi:10.1158/0008-5472.CAN-07-5997)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Lukacik P, Kavanagh KL & Oppermann U 2006 Structure and function of human 17β-hydroxysteroid dehydrogenases. Molecular and Cellular Endocrinology 248 6171. (doi:10.1016/j.mce.2005.12.007)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Luu-The V, Bélanger A & Labrie F 2008 Androgen biosynthetic pathways in the human prostate. Best Practice & Research Clinical Endocrinology & Metabolism 22 207221. (doi:10.1016/j.beem.2008.01.008)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Maier KG, Brandy K, Kittur D, Kort K & LaSpina M 2006 GPR30: a novel estrogen receptor expressed in aggressive prostate cancer. FASEB Journal 20 A221.

  • Mak P, Leav I, Pursell B, Bae D, Yang X, Taglienti CA, Gouvin LM, Sharma VM & Mercurio AM 2010 ERβ Impedes prostate cancer EMT by destabilizing HIF-1α and inhibiting VEGF-mediated snail nuclear localization: implications for gleason grading. Cancer Cell 17 319332. (doi:10.1016/j.ccr.2010.02.030)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Mak P, Li J, Samanta S & Mercurio AM 2015 ERβ regulation of NF-κB activation in prostate cancer is mediated by HIF-1. Oncotarget 6 4024740254. (doi:10.18632/oncotarget.5377)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Malkowicz SB 2001 The role of diethylstilbestrol in the treatment of prostate cancer. Urology 58 108113. (doi:10.1016/S0090-4295(01)01252-3)

  • Marcelli M, Ittmann M, Mariani S, Sutherland R, Nigam R, Murthy L, Zhao Y, DiConcini D, Puxeddu E, Esen A, et al.2000 Androgen receptor mutations in prostate cancer. Cancer Research 60 944949.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • McPherson SJ, Ellem SJ, Simpson ER, Patchev V, Fritzemeier K-H & Risbridger GP 2007 Essential role for estrogen receptorβin stromal-epithelial regulation of prostatic hyperplasia. Endocrinology 148 566574. (doi:10.1210/en.2006-0906)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • McTernan P, Anwar A, Eggo M, Barnett A, Stewart P & Kumar S 2000 Gender differences in the regulation of P450 aromatase expression and activity in human adipose tissue. International Journal of Obesity 24 875881. (doi:10.1038/sj.ijo.0801254)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Miftakhova R, Hedblom A, Semenas J, Robinson B, Simoulis A, Malm J, Rizvanov A, Heery DM, Mongan NP, Maitland NJ, et al.2016 Cyclin A1 and P450 aromatase promote metastatic homing and growth of stem-like prostate cancer cells in the bone marrow. Cancer Research 76 24532464. (doi:10.1158/0008-5472.CAN-15-2340)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Mo Z, Liu M, Yang F, Luo H, Li Z, Tu G & Yang G 2013 GPR30 as an initiator of tamoxifen resistance in hormone-dependent breast cancer. Breast Cancer Research 15 115.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Mohler JL, Gregory CW, Ford OH, Kim D, Weaver CM, Petrusz P, Wilson EM & French FS 2004 The androgen axis in recurrent prostate cancer. Clinical Cancer Research 10 440448. (doi:10.1158/1078-0432.CCR-1146-03)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Montgomery RB, Mostaghel EA, Vessella R, Hess DL, Kalhorn TF, Higano CS, True LD & Nelson PS 2008 Maintenance of intratumoral androgens in metastatic prostate cancer: a mechanism for castration-resistant tumor growth. Cancer Research 68 44474454. (doi:10.1158/0008-5472.CAN-08-0249)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Montico F, Hetzl AC, Cândido EM & Cagnon VHA 2013 Angiogenic and tissue remodeling factors in the prostate of elderly rats submitted to hormonal replacement. Anatomical Record 296 17581767. (doi:10.1002/ar.22786)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Mueller JW, Gilligan LC, Idkowiak J, Arlt W & Foster PA 2015 The regulation of steroid action by sulfation and desulfation. Endocrine Reviews 36 526563. (doi:10.1210/er.2015-1036)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Muir M, Romalo G, Wolf L, Elger W & Schweikert H-U 2004 Estrone sulfate is a major source of local estrogen formation in human bone. Journal of Clinical Endocrinology & Metabolism 89 46854692. (doi:10.1210/jc.2004-0049)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Murray R & Pitt P 1985 Treatment of advanced prostatic cancer, resistant to conventional therapy with aminoglutethimide. European Journal of Cancer and Clinical Oncology 21 453458. (doi:10.1016/0277-5379(85)90036-7)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Nakamura Y, Suzuki T, Fukuda T, Ito A, Endo M, Moriya T, Arai Y & Sasano H 2006 Steroid sulfatase and estrogen sulfotransferase in human prostate cancer. Prostate 66 10051012. (doi:10.1002/pros.20426)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Nelson AW, Tilley WD, Neal DE & Carroll JS 2014 Estrogen receptor beta in prostate cancer: friend or foe? Endocrine-Related Cancer 21 T219T234.

  • O’Dowd BF, Nguyen T, Marchese A, Cheng R, Lynch KR, Heng HHQ, Kolakowski Jr LF & George SR 1998 Discovery of three novel g-protein-coupled receptor genes. Genomics 47 310313. (doi:10.1006/geno.1998.5095)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Oduwole OO, Mäkinen MJ, Isomaa VV, Pulkka A, Jernvall P, Karttunen TJ & Vihko PT 2003 17β-Hydroxysteroid dehydrogenase type 2: independent prognostic significance and evidence of estrogen protection in female patients with colon cancer. Journal of Steroid Biochemistry and Molecular Biology 87 133140. (doi:10.1016/j.jsbmb.2003.08.008)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Parkin DM, Whelan SL, J F, L T & DB T 1997 Cancer Incidence in Five Continents. Lyon, France: International Agency for Research on Cancer Scientific Publications.

  • Parkin DM, Bray FI & Devesa SS 2001 Cancer burden in the year 2000. The global picture. European Journal of Cancer 37 (Supplement 8) 466. (doi:10.1016/S0959-8049(01)00267-2)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Piao Y-s, Wiesenfeld P, Sprando R & Arnold JT 2013 TGFβ1 alters androgenic metabolites and hydroxysteroid dehydrogenase enzyme expression in human prostate reactive stromal primary cells: Is steroid metabolism altered by prostate reactive stromal microenvironment? Journal of Steroid Biochemistry and Molecular Biology 138 206213. (doi:10.1016/j.jsbmb.2013.1005.1016)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Pilšáková L, Riečanský I & Jagla F 2010 The physiological actions of isoflavone phytoestrogens. Physiological Research/Academia Scientiarum Bohemoslovaca 59 651664.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Polari L, Yatkin E, Martínez Chacón MG, Ahotupa M, Smeds A, Strauss L, Zhang F, Poutanen M, Saarinen N & Mäkelä SI 2015 Weight gain and inflammation regulate aromatase expression in male adipose tissue, as evidenced by reporter gene activity. Molecular and Cellular Endocrinology 412 123130. (doi:10.1016/j.mce.2015.06.002)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Prins GS & Hu W-Y 2013 Stem Cells and Prostate Cancer. New York, NY, USA: Springer New York.

  • Prins GS, Huang L, Birch L & Pu Y 2006 The role of estrogens in normal and abnormal development of the prostate gland. Annals of the New York Academy of Sciences 1089 113. (doi:10.1196/annals.1386.009)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Prossnitz ER, Arterburn JB & Sklar LA 2007 GPR30: a G protein-coupled receptor for estrogen. Molecular and Cellular Endocrinology 265–266 138142. (doi:10.1016/j.mce.2006.12.010)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Prossnitz ER, Oprea TI, Sklar LA & Arterburn JB 2008a The ins and outs of GPR30: a transmembrane estrogen receptor. Journal of Steroid Biochemistry and Molecular Biology 109 350353. (doi:10.1016/j.jsbmb.2008.03.006)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Prossnitz ER, Sklar LA, Oprea TI & Arterburn JB 2008b GPR30: a novel therapeutic target in estrogen-related disease. Trends in Pharmacological Sciences 29 116123. (doi:10.1016/j.tips.2008.01.001)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Purohit A & Foster PA 2012 Steroid sulfatase inhibitors for estrogen- and androgen-dependent cancers. Journal of Endocrinology 212 99110. (doi:10.1530/JOE-11-0266)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Quaresma M, Coleman MP & Rachet B 2015 40-year trends in an index of survival for all cancers combined and survival adjusted for age and sex for each cancer in England and Wales, 1971–2011: a population-based study. Lancet 385 12061218. (doi:10.1016/S0140-6736(14)61396-9)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Raftogianis R, Creveling C, Weinshilboum R & Weisz J 2000 Chapter 6: estrogen metabolism by conjugation. JNCI Monographs 2000 113124. (doi:10.1093/oxfordjournals.jncimonographs.a024234)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Rago V, Romeo F, Giordano F, Ferraro A & Carpino A 2016 Identification of the G protein-coupled estrogen receptor (GPER) in human prostate: expression site of the estrogen receptor in the benign and neoplastic gland. Andrology 4 121127. (doi:10.1111/andr.12131)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Rajfer J & Coffey DS 1978 Sex steroid imprinting of the immature prostate. Long-term effects. Investigative Urology 16 186190.

  • Reed MJ, Purohit A, Woo LWL, Newman SP & Potter BVL 2005 Steroid sulfatase: molecular biology, regulation, and inhibition. Endocrine Reviews 26 171202. (doi:10.1210/er.2004-0003)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Reger M, Zollinger T, Liu Z, Jones J & Zhang J 2015 Abstract 1884: dietary intake of phytoestrogens and the risk of prostate cancer in the prostate, lung, colorectal, and ovarian cancer screening trial. Cancer Research 75 1884.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Risbridger GP, Davis ID, Birrell SN & Tilley WD 2010 Breast and prostate cancer: more similar than different. Nature Reviews. Cancer 10 205212. (doi:10.1038/nrc2795)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Robinson-Rechavi M, Garcia HE & Laudet V 2003 The nuclear receptor superfamily. Journal of Cell Science 116 585586. (doi:10.1242/jcs.00247)

  • Romanel A, Tandefelt DG, Conteduca V, Jayaram A, Casiraghi N, Wetterskog D, Salvi S, Amadori D, Zafeiriou Z, Rescigno P, et al.2015 Plasma AR and abiraterone-resistant prostate cancer. Science Translational Medicine 7 312re310312re310. (doi:10.1126/scitranslmed.aac9511)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • de Ronde W, van der Schouw YT, Muller M, Grobbee DE, Gooren LJG, Pols HAP & de Jong FH 2005 Associations of sex-hormone-binding globulin (SHBG) with non-SHBG-bound levels of testosterone and estradiol in independently living men. Journal of Clinical Endocrinology & Metabolism 90 157162. (doi:10.1210/jc.2004-0422)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Ross-Innes CS, Stark R, Teschendorff AE, Holmes KA, Ali HR, Dunning MJ, Brown GD, Gojis O, Ellis IO, Green AR, et al.2012 Differential oestrogen receptor binding is associated with clinical outcome in breast cancer. Nature 481 389393. (doi:10.1038/nature10730)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Roy J, Lefebvre J, Maltais R & Poirier D 2013 Inhibition of dehydroepiandosterone sulfate action in androgen-sensitive tissues by EM-1913, an inhibitor of steroid sulfatase. Molecular and Cellular Endocrinology 376 148155. (doi:10.1016/j.mce.2013.06.022)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Ryan CJ, Smith MR, de Bono JS, Molina A, Logothetis CJ, de Souza P, Fizazi K, Mainwaring P, Piulats JM, Ng S, et al.2013 Abiraterone in metastatic prostate cancer without previous chemotherapy. New England Journal of Medicine 368 138148. (doi:10.1056/NEJMoa1209096)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Sakr WA, Haas GP, Cassin BF, Pontes JE & Crissman JD 1993 The frequency of carcinoma and intraepithelial neoplasia of the prostate in young male patients. Journal of Urology 150 379385.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Samaras N, Frangos E, Forster A, Lang PO & Samaras D 2012 Andropause: a review of the definition and treatment. European Geriatric Medicine 3 368373. (doi:10.1016/j.eurger.2012.08.007)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Santen RJ, Thibault A, Myers C & Chung L 1997 Meeting summary: workshop conference on endocrine therapy of advanced prostate cancer, airlie house, November 3–4, 1996. Urologic Oncology: Seminars and Original Investigations 3 3138. (doi:10.1002/1097-0142(20011015)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Santen RJ, Petroni GR, Fisch MJ, Myers CE, Theodorescu D & Cohen RB 2001 Use of the aromatase inhibitor anastrozole in the treatment of patients with advanced prostate carcinoma. Cancer 92 20952101. (doi:10.1002/1097-0142(20011015)92:8<2095::aid-cncr1550>3.0.co;2-y)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Sarveswaran S, Gautam SC & Ghosh J 2012 Wedelolactone, a medicinal plant-derived coumestan, induces caspase-dependent apoptosis in prostate cancer cells via downregulation of PKCε without inhibiting Akt. International Journal of Oncology 41 21912199. (doi:10.3892/ijo.2012.1664)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Savoy RM & Ghosh PM 2013 The changing roles of steroid nuclear receptors with prostate cancer progression. Endocrine-Related Cancer 20 C9C11. (doi:10.1530/ERC-13-0193)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Scher HI, Fizazi K, Saad F, Taplin M-E, Sternberg CN, Miller K, de Wit R, Mulders P, Chi KN, Shore ND, et al.2012 Increased survival with enzalutamide in prostate cancer after chemotherapy. New England Journal of Medicine 367 11871197. (doi:10.1056/NEJMoa1207506)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Sharifi N & Auchus RJ 2012 Steroid biosynthesis and prostate cancer. Steroids 77 719726. (doi:10.1016/j.steroids.2012.03.015)

  • Siegel R, Naishadham D & Jemal A 2012 Cancer statistics, 2012. CA: A Cancer Journal for Clinicians 62 1029. (doi:10.3322/caac.20138)

  • Slavin S, Yeh C-R, Da J, Yu S, Miyamoto H, Messing EM, Guancial E & Yeh S 2014 Estrogen receptorαin cancer-associated fibroblasts suppresses prostate cancer invasion via modulation of thrombospondin 2 and matrix metalloproteinase 3. Carcinogenesis 35 13011309. (doi:10.1093/carcin/bgt488)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Smith MR, Kaufman D, George D, Oh WK, Kazanis M, Manola J & Kantoff PW 2002 Selective aromatase inhibition for patients with androgen-independent prostate carcinoma. Cancer 95 18641868. (doi:10.1002/cncr.10844)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Stanway SJ, Purohit A, Woo LWL, Sufi S, Vigushin D, Ward R, Wilson RH, Stanczyk FZ, Dobbs N, Kulinskaya E, et al.2006 Phase I study of STX 64 (667 Coumate) in breast cancer patients: the first study of a steroid sulfatase inhibitor. Clinical Cancer Research 12 15851592. (doi:10.1158/1078-0432.CCR-05-1996)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Strom SS, Yamamura Y, Duphorne CM, Spitz MR, Babaian RJ, Pillow PC & Hursting SD 1999 Phytoestrogen intake and prostate cancer: a case‐control study using a new database. Nutrition and Cancer 33 2025. (doi:10.1080/01635589909514743)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Szliszka E, Czuba ZP, Mertas A, Paradysz A & Krol W 2013 The dietary isoflavone biochanin-A sensitizes prostate cancer cells to TRAIL-induced apoptosis. Urologic Oncology: Seminars and Original Investigations 31 331342.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Takeuchi S, Takahashi T, Sawada Y, Iida M, Matsuda T & Kojima H 2009 Comparative study on the nuclear hormone receptor activity of various phytochemicals and their metabolites by reporter gene assays using chinese hamster ovary cells. Biological and Pharmaceutical Bulletin 32 195202. (doi:10.1248/bpb.32.195)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Takizawa I, Lawrence MG, Balanathan P, Rebello R, Pearson HB, Garg E, Pedersen J, Pouliot N, Nadon R, Watt MJ, et al.2015 Estrogen receptor alpha drives proliferation in PTEN-deficient prostate carcinoma by stimulating survival signaling, MYC expression and altering glucose sensitivity. Oncotarget 6 604616. (doi:10.18632/oncotarget)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Taneja SS, Morton R, Barnette G, Sieber P, Hancock ML & Steiner M 2013 Prostate cancer diagnosis among men with isolated high-grade intraepithelial neoplasia enrolled onto a 3-year prospective phase III clinical trial of oral toremifene. Journal of Clinical Oncology 31 523529. (doi:10.1200/JCO.2012.41.7634)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Taylor RA, Toivanen R, Frydenberg M, Pedersen J, Harewood L, Australian Prostate Cancer Bioresource, Collins AT, Maitland NJ & Risbridger GP 2012 Human epithelial basal cells are cells of origin of prostate cancer, independent of CD133 status. Stem Cells 30 1087–1096. (doi:10.1002/stem.1094)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Thomas P & Dong J 2006 Binding and activation of the seven-transmembrane estrogen receptor GPR30 by environmental estrogens: a potential novel mechanism of endocrine disruption. Journal of Steroid Biochemistry and Molecular Biology 102 175179. (doi:10.1016/j.jsbmb.2006.09.017)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Usui T 2006 Pharmaceutical prospects of phytoestrogens. Endocrine Journal 53 720. (doi:10.1507/endocrj.53.7)

  • Utsumi T, Yoshimura N, Takeuchi S, Maruta M, Maeda K & Harada N 2000 Elevated steroid sulfatase expression in breast cancers. Journal of Steroid Biochemistry and Molecular Biology 73 141145. (doi:10.1016/S0960-0760(00)00060-1)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Vidal AC, Howard LE, Moreira DM, Castro-Santamaria R, Andriole GL & Freedland SJ 2014 Obesity increases the risk for high-grade prostate cancer: results from the REDUCE study. Cancer Epidemiology, Biomarkers & Prevention 23 29362942.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Wang F, Vihma V, Soronen J, Turpeinen U, Hämäläinen E, Savolainen-Peltonen H, Mikkola TS, Naukkarinen J, Pietiläinen KH, Jauhiainen M, et al.2013 17β-Estradiol and estradiol fatty acyl esters and estrogen-converting enzyme expression in adipose tissue in obese men and women. Journal of Clinical Endocrinology & Metabolism 98 49234931. (doi:10.1210/jc.2013-2605)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Wernert N, Kern L, Heitz P, Bonkhoff H, Goebbels R, Seitz G, Inniger R, Remberger K & Dhom G 1990 Morphological and immunohistochemical investigations of the utriculus prostaticus from the fetal period up to adulthood. Prostate 17 1930. (doi:10.1002/pros.2990170104)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • White BA, Porterfield SP & Porterfield SP 2013 Endocrine and Reproductive Physiology. Philadelphia, PA, USA: Elsevier/Mosby.

  • Whittemore AS, Kolonel LN, Wu AH, John EM, Gallagher RP, Howe GR, Burch JD, Hankin J, Dreon DM, West DW, et al.1995 Prostate cancer in relation to diet, physical activity, and body size in blacks, whites, and Asians in the United States and Canada. Journal of the National Cancer Institute 87 652661. (doi:10.1093/jnci/87.9.652)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Wright JL, Kwon EM, Ostrander EA, Montgomery RB, Lin DW, Vessella R, Stanford JL & Mostaghel EA 2011 Expression of SLCO transport genes in castration-resistant prostate cancer and impact of genetic variation in SLCO1B3 and SLCO2B1 on prostate cancer outcomes. Cancer Epidemiology Biomarkers & Prevention 20 619627.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Yamnik RL & Holz MK 2010 mTOR/S6K1 and MAPK/RSK signaling pathways coordinately regulate estrogen receptorαserine 167 phosphorylation. FEBS Letters 584 124128. (doi:10.1016/j.febslet.2009.11.041)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Yang M, Kenfield SA, Blarigan ELV, Kasperzyk JL, Sesso HD, Ma J, Stampfer M & Chavarro JE 2014 Abstract 1263: dietary patterns after prostate cancer diagnosis in relation to disease-specific and total mortality. Cancer Research 74 1263.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Yeh C-R, Da J,