Oestrogen receptor β is required for androgen-stimulated proliferation of LNCaP prostate cancer cells

Abstract

The role of oestrogens in the development of prostate cancer is poorly understood. However, a large body of evidence has suggested that oestrogenic hormones may be involved in prostatic malignancy. The localization of oestrogen receptor β (ERβ) in the secretory epithelium of the human prostate has raised the intriguing possibility that the action of oestrogen could be mediated, at least in part, by this receptor during the process of carcinogenesis. Hence, specific interference with oestrogen-activated and ERβ-mediated transcriptional activity could open new issues in the endocrine manipulation of prostate tumours. In the present study, we provide new insights into the role of ERβ in the context of an androgen-responsive prostate cancer cell line such as LNCaP, which was used as a model system together with steroid receptor negative HeLa cells. ERβ and the mutated androgen receptor (AR) T877A did not discriminate between oestrogen- or androgen-induced transactivation, whereas ERβ and AR transcriptional activity were inhibited only by the respective hormone antagonists ICI 182,780 and casodex. Furthermore, the nuclear localization of ERβ evaluated by immunocytochemistry confirmed the promiscuous response to hormones in addition to the specific inhibitory action of antagonists. Interestingly, ICI 182,780 and an ERβ antisense expression vector repressed the growth effects of both 17β-oestradiol and 5α-dihydrotestosterone, suggesting that ERβ has a key role in the proliferation induced by these steroids in LNCaP prostate cancer cells. Thus our findings implicate ERβ as a potential target for the treatment of prostate tumours. © 2004 Society for Endocrinology.