Involvement of estrogen receptors in prostatic diseases

Abstract

Abbreviations & Acronyms 3,4-QE2 = estradiol-3,4,quinone 3b-adiol = 5a-androstane-3b, 17b-diol 4-OHE2 = 4-hydroxyestradiol 17b-HSD VII = 17b-hydroxysteroid dehydrogenase type 7 AR = androgen receptor ArKO = aromatase-knockout BP = DL-2-[4-(2-piperidinoethoxy) phenyl]-3-phenyl-2 H-1-benzopyran BPH = benign prostatic hyperplasia CRPC = castration-resistant prostate cancer DES = diethylstilbestrol DHT = dihydrotestosterone E2 = estradiol EBAG9 = estrogen receptor-binding fragment-associated gene 9 EMT = epithelial-mesenchymal transition ER = estrogen receptor ERaKO = estrogen receptor a knockout ERbKO = estrogen receptor b knockout ERE = estrogen-responsive element ERG = v-ets erythroblastosis virus E26 oncogene homolog (avian) ERR = estrogen receptor-related receptors hERb = human estrogen receptor b HGPIN = high-grade prostatic intraepithelial neoplasia HIF-1a = hypoxia inducible factor 1a IGF-1 = insulin-like growth factor 1 KLF-5 = Krüppel-like zinc finger transcription factor 5 NFk = nuclear factor k NFkB = nuclear factor kB OHT = 4-hydroxytamoxifen PGC-1 = peroxisome proliferator-activated receptor g coactivator 1 PIN = prostatic intraepithelial neoplasia PrSC = prostatic stromal cells PSA = prostate-specific antigen RT-PCR = reverse transcription polymerase chain reaction SERM = selective estrogen receptor modulators TGFb = transforming growth factor b TMPRSS2 = transmembrane protease serine 2 VEGF-A = vascular endothelial growth factor A Abstract: Accumulating evidence shows that estrogens participate in the pathogenesis and development of benign prostatic hyperplasia and prostate cancer by activating estrogen receptor a. In contrast, estrogen receptor b is involved in the differentiation and maturation of prostatic epithelial cells, and thus possesses antitumor effects in prostate cancer. However, the natural ligands of estrogen receptor b are not fully understood , and its mode of action according to its ligands and the binding sites located in the promoter regions of downstream genes remains to be elucidated. Here, we review recent experimental investigations of estrogen receptors and their urological relevance. Estrogen receptor-mediated signaling in the prostate is essential together with the androgen receptor-mediated pathway, providing a new therapeutic target for prostatic diseases.

Expression of Androgen and Estrogen Signaling Components and Stem Cell Markers to Predict Cancer Progression and Cancer-Specific Survival in Patients with Metastatic Prostate Cancer

“…7), forkhead-box (FOX) family proteins (8)(9)(10)(11), octameter transcription factor (Oct1; ref. 12), and ERs (5,13,14). However, the distribution and functions of these steroid nuclear receptors vary depending on the sites from which prostate cancer samples are obtained (13)(14)(15).…”

“…12), and ERs (5,13,14). However, the distribution and functions of these steroid nuclear receptors vary depending on the sites from which prostate cancer samples are obtained (13)(14)(15). For example, the AR gene is expressed in luminal, basal, and stromal cells.…”

Deficiency of ERβ and prostate tumorigenesis in FGF8b transgenic mice

“…Several studies have provided evidence for antiproliferative and differentiation-promoting effects of ERb and tumorigenic effects of ERa in the prostate (Prins et al 2001, Risbridger et al 2001, McPherson et al 2007, Savolainen et al 2007, Ricke et al 2008, Kawashima & Nakatani 2012). Recently, the anti-tumorigenic effect of ERb was supported by results from a study, which compared the incidence of prostate tumorigenesis in genistein-and casein-fed transgenic adenocarcinoma of the mouse prostate (TRAMP), BERKO-TRAMP, and ERKO-TRAMP mice (Slusarz et al 2012).…”

Editorial Comment to Involvement of estrogen receptors in prostatic diseases

“…1 Since the discovery of ERb in the rat prostate, the two types of ER, ERa and ERb, have been believed to play distinct roles in the prostate, as an "accelerator and brake", respectively. Actually, accumulating data strongly suggest the antiproliferative effects of wild-type ERb (ERb1) in benign and malignant prostatic tissue.…”