title: Oestrogen receptor beta 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 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.
authors.affiliation: Department of Pharmaco-Biology, University of Calabria, 87036 Rende (CS), Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Maggiolini
authors.forename: Anna Grazia
authors.initials: AG
authors.lastname: Recchia
authors.forename: Amalia
authors.initials: A
authors.lastname: Carpino
authors.forename: Adele
authors.initials: A
authors.lastname: Vivacqua
authors.forename: Giovanna
authors.initials: G
authors.lastname: Fasanella
authors.forename: Vittoria
authors.initials: V
authors.lastname: Rago
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Pezzi
authors.forename: Pierre-André
authors.initials: PA
authors.lastname: Briand
authors.forename: Didier
authors.initials: D
authors.lastname: Picard
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Andò
mesh_terms: 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
chemical_list: 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