Differential response of an ovarian-responsive mouse mammary tumor to androgenic and estrogenic agents.
An ovarian-responsive mammary tumor subline, T4-OR26, was isolated from an outgrowth of a progressed TPDMT-4 pregnancy-dependent mammary tumor in a virgin DDD mouse. T4-OR26 tumors were characterized by significantly faster growth in virgin mice than in ovariectomized mice. Both estrogen and progesterone were important for growth of the subline, as they were for that of the parent. Tamoxifen (TAM), with estrogenic activity, and epithiostanol (EPI) and testosterone propionate, with androgenic activity, which all caused TPDMT-4 tumors to regress, were compared for antitumor potency against the new subline by 3 s.c. injections weekly in virgins. EPI at 300 micrograms and testosterone propionate at 1000 micrograms elicited immediate tumor growth suppression with subsequent slight regression as did ovariectomy. TAM at 1000 micrograms caused tumor growth suppression after 2 weeks without subsequent regression. At 600 micrograms, EPI but not TAM significantly inhibited 17 beta-estradiol plus progesterone-induced tumor growth; at 400 micrograms, neither had any significant effect on the tumor growth induced by 17 beta-estradiol alone. With regard to their effect on hormone receptors, it was noted that EPI and testosterone propionate treatments with tumor regression caused significant reduction in cytoplasmic progesterone receptor, but TAM treatment, which does not influence tumor growth, did not cause such reduction. The results provide evidence that hormone-dependent mammary tumors may acquire greater resistance to estrogenic than to androgenic therapeutics with progression.
D000732:Androstanols / Q000494:pharmacology*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000473:pathology*; D051379:Mice; D011374:Progesterone / Q000494:pharmacology; D011959:Receptors, Estradiol; D011960:Receptors, Estrogen / Q000187:drug effects; D011980:Receptors, Progesterone / Q000187:drug effects; D013629:Tamoxifen / Q000494:pharmacology*; D013739:Testosterone / Q000494:pharmacology*
D000732:Androstanols; D011959:Receptors, Estradiol; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013629:Tamoxifen; D013739:Testosterone; D011374:Progesterone; D004958:Estradiol; C002976:epitiostanol