STEROID STIMULATION OF PLASMINOGEN-ACTIVATOR PRODUCTION IN A HUMAN-BREAST CANCER CELL-LINE (MCF-7)

Abstract

The production of plasminogen activator by the human breast cancer cell line MCF-7 was stimulated by physiological concentrations of estradiol [E2] under conditions where the growth of the cells was neither dependent on nor stimulated by E2. Stimulation was measurable within 8 h after the addition of E2 and was evident in both the level of plasminogen activator released into the culture medium and the level within the cells. The level of production varied with cell density, but production was stimulated by E2 at all densities tested. The antiestrogen tamoxifen inhibited estrogen stimulation, and this inhibition could be overcome by increased concentrations of E2. Production was also stimulated by progesterone and could be stimulated by lower levels of progesterone in cells pretreated with E2 or tamoxifen, both of which have been reported to increase the level of progesterone receptor in these cells. Estrogen reportedly is essential and progesterone is stimulatory for the formation of tumors by MCF-7 cells in athymic mice. The ability of these same 2 hormones to stimulate the production of plasminogen activator by these cells, under conditions where they have no effect on cell growth raises the possibility that estrogen may not play a mitogenic role in the growth of these tumors. Rather, it may support tumor growth by inducing the cells to produce products, such as plasminogen activator, and possibly take on other characteristics essential to the malignant state.