Effect of estrogens and antiestrogens on growth-regulatory enzymes in human breast cancer cells in tissue culture

Abstract

The effect of estrogens and antiestrogens is examined on three enzymes the activities of which are known to correlate with cell growth. Estrogen treatment increases thymidylate synthetase binding sites up to 4-fold over controls. The extent of induction is dependent on incubation time and the basal rate of cell growth in untreated cells. Amount of active enzyme generally shows a positive correlation with rates of DNA synthesis and cell growth. Thymidine kinase activity and the number of dihydrofolate reductase binding sites are similarly induced by estrogen treatment. Conversely, the effect of antiestrogens on MCF-7 cells is exceedingly complex in that responses in enzyme activities and several generally accepted indices of cell growth (cell number, protein content, rate of DNA synthesis) are dissimilar. Dose response, magnitude of response, and direction of response (increase or decrease) are distinct for each enzyme and for each measure of cell growth with each antiestrogen tested. These results suggest that specific cellular activities are modulated independently by estrogens and antiestrogens and that changes in ligand-receptor complex cannot be the sole explanation for the specificity of estrogen and antiestrogen action. Some degree of specificity and heterogeneity may reside at the level of receptor interaction with the various genes subject to estrogenic modulation.