title: Divergent biological effects of estradiol and diethylstilbestrol in the prostate cancer cell line MOP.
abstract: The involvement of mutated androgen receptors (mut-AR) in the actions of estrogens in prostate cancer cells is controversial. This work was designed to determine the role of such receptors in the growth inhibition by estradiol (E2) and androgens of the MOP cell line, a derivative of the LNCaP cell line. Diethylstilbestrol (DES) was used as a "tool". E2 like DHT and R1881 inhibits MOP cell proliferation while DES does not. E2 and R1881 down regulate mut-AR mRNA, DES does not. E2 enhances mut-AR transcriptional activity less efficiently than R1881 while DES does not. E2 and R1881 up regulate PSA secretion in a dose-dependent manner, DES does it marginally at 10(-6)M. MOP cells express low amounts of ERalpha and ERbeta mRNA but neither DES nor E2 and R1881 do enhance ER transcriptional activity. DES and E2 bind to mut-AR with relative binding affinities which are respectively 1/175 and 1/10 that of DHT. The E2 and androgen-repressed proliferation is prevented by DES and by the anti-androgen bicalutamide. In LNCaP cells, DES prevents the androgen-enhanced proliferation. These results strongly suggest that: (a) the putative endogenous ERs are biologically inactive in MOP cells, (b) the E2-repressed proliferation results from hormone binding to mut-AR and, (c) DES is an anti-androgen in mut-AR expressing cell line.
authors.affiliation: INSERM U407, Oullins, Faculté de Médecine Lyon-Sud, BP 12, 165 Chemin du Grand Revoyet, 69 921 Oullins Cédex, France.
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Kalach
authors.forename: Marie-Odile
authors.initials: MO
authors.lastname: Joly-Pharaboz
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Chantepie
authors.forename: Brigitte
authors.initials: B
authors.lastname: Nicolas
authors.forename: Françoise
authors.initials: F
authors.lastname: Descotes
authors.forename: Claire
authors.initials: C
authors.lastname: Mauduit
authors.forename: Mohamed
authors.initials: M
authors.lastname: Benahmed
authors.forename: Jean
authors.initials: J
authors.lastname: André
mesh_terms: D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D004054:Diethylstilbestrol / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology*; D006801:Humans; D008297:Male; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011471:Prostatic Neoplasms; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
chemical_list: D011944:Receptors, Androgen; D004958:Estradiol; D004054:Diethylstilbestrol; D017430:Prostate-Specific Antigen