Effects of serum and insulin on the sensitivity of the human breast cancer cell line MCF-7 to estrogen and antiestrogens.

The effect of the antiestrogens tamoxifen and nafoxidine on the growth of the human breast cancer cell line MCF-7 is modified by both serum and insulin. Tamoxifen inhibition of the growth of MCF-7 cells in culture is reduced as the concentration of serum in the medium is increased from 0.1% to 5 to 10%. Estradiol does not stimulate cell growth over the same range of serum levels. Insulin changes the sensitivity of MCF-7 cells to both estrogen and antiestrogens. Cells growing in media containing insulin are less sensitive to inhibition by either tamoxifen or nafoxidine than are cells growing in its absence. In addition, higher concentrations of estradiol are required to stimulate the production of plasminogen activator when cells are grown in media containing insulin. This effect of insulin can be accounted for by the finding that insulin lowers the level of estrogen receptor in MCF-7 cells without altering the binding constant for the hormone. Cells grown with insulin have an average of 21,000 +/- 4,700 (S.D.) estrogen binding sites/cell compared to 62,000 +/- 9,700 sites/cell in cells grown in the absence of insulin. This difference in receptor level is sufficient to account for the difference in the concentration of estradiol needed for equivalent induction of plasminogen activator in cultures with or without insulin. These results indicate that the level of estrogen receptor in breast cancer cells can be changed and that the sensitivity of such cells, both to estrogen and to antiestrogens, is altered by changes in the level of estrogen receptor. They also have implications concerning the mechanism by which antiestrogens act to inhibit the growth of mammary tumor cells.