Estrogen responsive proliferation of clonal human breast carcinoma cells in athymic mice

A clone of MCF-7 (MCF-7ED), a cell in continuous in vitro cultivation derived from an estrogen-responsive human breast carcinoma, requires estrogen supplementation for progressive exponential (doubling time: 50–85 h) tumor growth in the mammary fat of athymic mice. The plasma concentration of estradiol which stimulated exponential growth of MCF-7ED corresponded to physiologic premenopausal levels in women. The tumors were carcinomas with murine and MCF-7ED cells intermixed. MCF-7ED cells could be repurified in subcultures of mixed tumors. Comparative studies of breast and non-breast cell lines showed concordance between the presence of estradiol receptor, sensitivity to the anti-estrogen tamoxifen for growth in vitro, and estradiol dependence for tumorigenic growth in athymic mice. Progesterone alone did not stimulate MCF-7ED growth, but acted synergistically with estrogen. Progesterone's action was to decrease tumor latent period, not to increase final tumor incidence or growth rate. Under estrogen-deficient conditions, conditions approximating postmeno-pausal status in women, (10^?10 M in plasma), a dormant state was established between MCF-7ED cells and murine mammary stroma which could be maintained several months. The dormant state could be broken by introduction of estradiol, but not progesterone. This system should be useful for defining host and cancer cell determinants in estrogen-responsive breast cancer growth.