Role of hormones in the growth and regression of human breast cancer cells (MCF-7) transplanted into athymic nude mice.

The hormonal environments require by human breast cancer cells MCF-7 to produce solid tumors in nude mice are described. A 100% take was obtained within 7 days following inoculation of 2X10(6) actively growing (log phase) MCF-7 cells into the mammary fat pads of intact, athymic BALB/c nude mice. Tumors failed to develop, even with an inoculum of 20X10(6) cells/mouse, in ovariectomized mice or in mice made diabetic with streptozotocin and observed for 90 days after cell inoculation. A 100% incidence of tumors was obtained in mice that were either hypophysectomized or made diabetic but received injections of 0.2 IU insulin/day/mouse. A 100% incidence of tumors was also obtained in ovariectomized mice that received 17 beta-estradiol in the form of a pellet placed subcutaneously in the interscapular region at the time of cell inoculation. Palpable tumors also developed in ovariectomized mice treated with prolactin, perphenazine, estrone, or estriol, but no takes were observed in ovariectomized mice treated with progesterone, 5 alpha-dihydrotestosterone, or hydrocortisone. Growth of the MCF-7 tumor was stimulated five- to sixfold in both intact and hypophysectomized mice that each received a 17 beta-estradiol pellet. Removal of the 17 beta-estradiol pellets form tumor-bearing ovariectomized mice failed to induce tumor regression. Tumors that continued to grow in ovariectomized mice deprived of 17 beta-estradiol regressed by 50% or more of their initial volume when tamoxifen was injected for 7 days at 5 micrograms/mouse/day) +/- theophyline (1 mg/mouse/day), tumor growth arrest was observed during the 2-to 3-week treatment period. Streptozotocin-induced diabetes in tumor-bearing mice always resulted in complete tumor regression following a 3-week treatment period.