Differential expression of estrogen-related receptors b and c (ERRb and ERRc) and their clinical significance in human prostate cancer.

Estrogen-signaling pathways in addition to androgen-signalingpathways are implicated in the development of prostatecancer (PCa).(1) Diethylstilbestrol (DES) was previously usedfor endocrine therapy in the treatment of PCa. Presently, selectiveestrogen receptor modulators (SERMs) are being used forthis therapy. Toremifene, an estrogen receptor a (ERa) modulator,is used in patients with high-grade intraepithelial neoplasia(HGPIN) for the prevention of PCa, while raloxifene, an ERbmodulator, is used in patients with hormone-refractory PCa.(2,3)The biological activities of these chemicals are mediated by twoERs – ERa and ERb. Since ERa is predominantly localized inthe stromal cells of the prostate,(4–7) the ERa-mediated effectsof estrogens on the prostatic epithelium are thought to be mediatedby paracrine pathways. In contrast, ERb is predominantlylocalized in the epithelial cells of the normal human prostate.ERb expression is lesser in PCa than in benign epithelium.(4,8)Thus, ERb exhibits a protective effect against aberrant cellproliferation and carcinogenesis.(9–12)Recent studies have focused on additional