Estrogen inhibition of a Mr 39,000 glycoprotein secreted by human breast cancer cells.

We have identified a secreted glycoprotein with an apparent molecular weight of 39,000 that is inhibited by estrogens and stimulated by antiestrogens in the MCF-7 human breast cancer cell line. The protein was detected within 24 h of hormone treatment with inhibition occurring at concentrations as low as 10(-11) M estradiol and stimulation occurring with antiestrogens. When phenol red, which has been found to have estrogenic activity, is removed from the tissue culture medium, no inhibition of cell growth or induction of the Mr 39,000 protein is seen with antiestrogens. A 6-fold decrease in the amount secreted in the presence of estrogens is seen under these conditions. The induction was specific in that growth inhibition by several other means did not induce expression of the Mr 39,000 protein. The Mr 39,000 protein has been identified as a glycoprotein complex that can be resolved into four polypeptides with two major components that migrate in the pH range of 5.5 to 6.3 by two-dimensional gel electrophoresis. This protein is the first evidence that estrogens inhibit a specific protein and it may prove useful as a marker of antiestrogen-induced growth arrest in breast cancer.