Growth-stimulating Effect of Pharmacological Doses of Estrogen on Androgen-dependent Shionogi Carcinoma 115 in Vivo but not in Cell Culture

Abstract Shionogi carcinoma 115 (SC115) had been accepted for 20 years as an androgen-dependent mouse mammary tumor, the growth of which is stimulated only by androgen. However, we very recently found that the growth of SC115 tumors in vivo is stimulated not only by physiological doses of androgen but also by pharmacological doses of estrogen through the estrogen receptor system. In the present study, the growth-stimulative effect of estrogen on an androgen-dependent cloned cell line (SC-3) derived from SC115 cells, which showed androgen- and estrogen-dependent growth in vivo , was examined in vitro . In serum-supplemented medium (Eagle9s minimum essential medium containing 2% steroid-free fetal calf serum), testosterone or 5α-dihydrotestosterone (10 -9 –10 -6 m) significantly stimulated the growth of SC-3 cells (3.2-fold increase in cell number at day 10 in culture containing 10 -8 m androgens) and changed the shape of SC-3 cells from epithelial to spindle (fibroblast-like), whereas 17β-estradiol (10 -12 –10 -6 m) even in high concentrations had no such effects on SC-3 cells. Contrary to the effect of 17β-estradiol in vivo , 17β-estradiol as well as cyproterone acetate (10 -8 –10 -6 m) inhibited the growth-stimulative effect of testosterone (10 -8 m) on SC-3 cells in a dose-dependent manner in the serum-supplemented medium. The anti-androgen and 17β-estradiol also showed comparable competitive effects on [ 3 H]testosterone binding to androgen receptor in SC-3 cells. In serum-free medium [Ham9s F-12:Eagle9s minimum essential medium (1:1, v/v) containing 0.2% bovine serum albumin], testosterone [10 -8 m] also markedly stimulated the growth of spindle-shaped SC-3 cells, and epidermal growth factor (1 ng/ml) enhanced the growth-stimulative effect of testosterone, whereas 17β-estradiol (10 -8 –10 -6 m) in the absence or presence of epidermal growth factor had no growth-stimulative effect on SC-3 cells. We conclude that the growth of SC115 cells is stimulated by either physiological doses of androgen or pharmacological doses of estrogen in vivo but only by androgen in cell culture.