MCF.7Ca and MCF.7Cc cells grew faster in intact mice than In ovariec

MCF-7 cells transfected with human placental aromatase gene (MCF 7Ca cells) or cells transfected with plasmid vector only (MCF-7Cc cells) were inoculated into nude mice with MatrigeL Tumors formed from both MCF.7Ca and MCF.7Cc cells grew faster in intact mice than In ovariec tomized mice, suggesting that the tumors maintained their responsiveness to estrogen stimulation and that their growth was supported by ovarian estrogen. Injections of androstenedione (0.1 mg/mouse/day) to provide the substrate for aromatization to ovariectomized mice bearing MCF-7Ca tumors accelerated their growth but did not affect growth of MCF-7Cc tumors. This result indicates that local production of estrogen by Intra twnoral aromatase was sufficient to stimulate tumor growth. When ovari ectomized mice with MCF.7Ca tumors supplemented with androstenedi one were treated with aromatase inhibitors 4-hydroxyandrostenedione (1 mg/mouse/day, s.c.) or CGS 16949A (0.5 mg/mouse/day, s.c), or with the antiestrogen tamoxifen (10 pg/mouse/day, s.c.), tumor growth was signif icantly inhibited. Tumor aromatase activity measured at the end of treat ment was also inhibited by 4-hydroxyandrostenedione when the mice were sacrificed 4 h after the last injection. The tumors of this mouse model are dependent for their growth on estrogens from an endogenous nonovarian source. Thus, it simulates the situation in the postmenopausal breast cancer patient and could be used to evaluate the effect of aromatase inhibitors and antiestrogens.