Anti-glucocorticoids block the enhancement of mouse mammary tumor virus production by 12-O-tetradecanoylphorbol-13-acetate.
Four anti-glucocorticoids, 11-deoxycortisol, deoxycorticosterone, 17 alpha-methyltestosterone and progesterone were demonstrated to antagonize the stimulation of mouse mammary tumor virus (MMTV) production by the glucocorticoid hormone dexamethasone in the cell line Mm5mt. These same anti-glucocorticoids were also able to suppress the enhancement of MMTV production by the tumor promoting phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), whereas estradiol, the anti-tumor promoter trans-retinoic acid, and the calmodulin inhibitor, chlorpromazine did not. Binding competition studies indicate that TPA can compete with dexamethasone in binding to the cellular glucocorticoid receptor. These results suggest that TPA stimulates the expression of MMTV by mimicking a glucocorticoid hormone.
D000818:Animals; D001667:Binding, Competitive; D002273:Carcinogens; D002460:Cell Line; D002746:Chlorpromazine / Q000494:pharmacology; D003350:Cortodoxone / Q000494:pharmacology; D003900:Desoxycorticosterone / Q000494:pharmacology; D003907:Dexamethasone / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology; D005938:Glucocorticoids / Q000037:antagonists & inhibitors*; D007700:Kinetics; D008325:Mammary Neoplasms, Experimental; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics*; D008777:Methyltestosterone / Q000494:pharmacology; D051379:Mice; D008809:Mice, Inbred C3H; D010704:Phorbols / Q000494:pharmacology*; D011374:Progesterone / Q000494:pharmacology; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D002273:Carcinogens; D005938:Glucocorticoids; D010704:Phorbols; D011965:Receptors, Glucocorticoid; D003900:Desoxycorticosterone; D011374:Progesterone; D004958:Estradiol; D003907:Dexamethasone; D013755:Tetradecanoylphorbol Acetate; D002746:Chlorpromazine; D008777:Methyltestosterone; D003350:Cortodoxone