A new nude mouse model for postmenopausal breast cancer using MCF-7 cells transfected with the human aromatase gene.
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 ovariectomized 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 intratumoral aromatase was sufficient to stimulate tumor growth. When ovariectomized mice with MCF-7Ca tumors supplemented with androstenedione 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 micrograms/mouse/day, s.c.), tumor growth was significantly inhibited. Tumor aromatase activity measured at the end of treatment 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.
Yue
W
W
Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore 21201.
Zhou
D
D
Chen
S
S
Brodie
A
A
D000735:Androstenedione / Q000494:pharmacology; D000818:Animals; D001141:Aromatase / Q000235:genetics*; D047072:Aromatase Inhibitors; D004195:Disease Models, Animal; D004965:Estrogen Antagonists / Q000627:therapeutic use; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010052:Ovariectomy; D017698:Postmenopause; D014162:Transfection; D014407:Tumor Cells, Cultured
D047072:Aromatase Inhibitors; D004965:Estrogen Antagonists; D000735:Androstenedione; D001141:Aromatase