Oestrogen receptor beta is required for androgen-stimulated proliferation of LNCaP prostate cancer cells.
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 beta (ERbeta) 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 ERbeta-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 ERbeta 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. ERbeta and the mutated androgen receptor (AR) T877A did not discriminate between oestrogen- or androgen-induced transactivation, whereas ERbeta and AR transcriptional activity were inhibited only by the respective hormone antagonists ICI 182,780 and casodex. Furthermore, the nuclear localization of ERbeta evaluated by immunocytochemistry confirmed the promiscuous response to hormones in addition to the specific inhibitory action of antagonists. Interestingly, ICI 182,780 and an ERbeta antisense expression vector repressed the growth effects of both 17beta-oestradiol and 5alpha-dihydrotestosterone, suggesting that ERbeta has a key role in the proliferation induced by these steroids in LNCaP prostate cancer cells. Thus our findings implicate ERbeta as a potential target for the treatment of prostate tumours.
Maggiolini
Marcello
M
Department of Pharmaco-Biology, University of Calabria, 87036 Rende (CS), Italy.
Recchia
Anna Grazia
AG
Carpino
Amalia
A
Vivacqua
Adele
A
Fasanella
Giovanna
G
Rago
Vittoria
V
Pezzi
Vincenzo
V
Briand
Pierre-André
PA
Picard
Didier
D
Andò
Sebastiano
S
D000726:Androgen Antagonists / Q000378:metabolism; D000728:Androgens / Q000378:metabolism*; D000813:Anilides / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D013196:Dihydrotestosterone / Q000378:metabolism; D004958:Estradiol / Q000031:analogs & derivatives* / Q000378:metabolism; D004965:Estrogen Antagonists / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism*; D000077267:Fulvestrant; D017930:Genes, Reporter; D006801:Humans; D008297:Male; D009570:Nitriles; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism*; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D020218:Response Elements; D014105:Tosyl Compounds
D000726:Androgen Antagonists; D000728:Androgens; D000813:Anilides; D004965:Estrogen Antagonists; D047629:Estrogen Receptor beta; D009570:Nitriles; D016376:Oligonucleotides, Antisense; D011944:Receptors, Androgen; D014105:Tosyl Compounds; D013196:Dihydrotestosterone; D000077267:Fulvestrant; D004958:Estradiol; C053541:bicalutamide