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.