CONTROL OF CELL-PROLIFERATION OF HUMAN BREAST MCF7 CELLS - SERUM AND ESTROGEN RESISTANT VARIANTS

The hypothesis explored in this article states that the control of the proliferation of estrogen target cells is regulated through two steps : the first involves a proliferative event in which estrogens cancel t he inhibition exerted by a plasma-borne protein, and the second, an es trogen-induced proliferative shutoff [1]. To study these estrogen-medi ated events we developed a series of variants of the human breast MCF7 cell line. A first variant was selected by requiring the ancestral MC F7 cells to proliferate initially in Dulbecco's modified Eagle's pheno l red-free medium supplemented with 5% charcoal-dextran stripped fetal calf serum; after 4 months, surviving cells were switched to 10% char coal-dextran stripped human serum. Five months later; a stable cell li ne was characterized and cloned having a phenotype that allowed for ma ximal proliferation in charcoal-dextran stripped human serum-supplemen ted medium (CDHuS) to which no estradiol was added. Estradiol concentr ations above 0.3 nM inhibited the proliferation of these cells; this e ffect was estrogen-specific. These cells are called E8CASS. A second v ariant derived from E8CASS cells was selected in 5% CDHuS supplemented with 0.3 nM estradiol; the proliferative pattern of these cells was c omparable to that of the ancestral MCF7 cells. These revertant cells a re called A2E8CASS. All variants and the ancestral MCF7 cells have fun ctional estrogen receptors, as evidenced by the estrogen-induced expre ssion of a pS2-CAT reporter gene. In conclusion, the collected data ar e compatible with the idea that, in MCF7 breast cells, the estradiol-m ediated proliferative component can be segregated from the inhibitory effect also generated by estradiol.