Mechanism of estrogen action on cellular proliferation: evidence for indirect and negative control on cloned breast tumor cells.

Human MCF7 breast tumor cells grew as estrogen-dependent tumors in nude mice. In contrast, they were not estrogen-dependent for proliferation in serumless culture media. Charcoal-dextran stripped female human serum supplemented media (5% to 40%) inhibited their proliferation in a dose dependent pattern. Estrogens reversed this inhibition. Concentrations of 2% of this serum allowed for maximal yield regardless of the presence of estrogens. Charcoal-dextran stripped fetal bovine serum was also inhibitory but less potent than the human serum. Non-estrogenic steroids, insulin, epidermal growth factor and transferrin failed to overcome the inhibitory effect of human serum. These results suggest that 1) human and bovine sera contain an inhibitor of the proliferation of estrogen-sensitive cells, and 2) estrogens promote cell proliferation by neutralizing this serum-borne inhibitor.