Effects of estrogen and antiestrogen on DNA polymerase in human breast cancer.
We have investigated the effects of estrogens and antiestrogens on cellular DNA-dependent DNA polymerase activity in human breast cancer, using as a model the MCF-7 human breast cancer cell line which contains estrogen receptor. 17 beta-Estradiol had little if any effect on cytosol DNA polymerase activity or growth (total DNA per flask) of MCF-7 cells. Incubation of the cells for 4 to 6 days with the antiestrogen nafoxidine, however, resulted in a dose-dependent reduction in cytosol DNA polymerase activity to one-half that observed in untreated cells. Enzyme activity in antiestrogen-treated cells was restored to levels contained in untreated cells by removing antiestrogen from the growth medium and incubating the cells for an additional 4 days with 17 beta-estradiol. The restoration required estrogenic steroids specifically, and the time course, magnitude, and dose dependence of the response were similar to estrogen-stimulated increases in DNA polymerase activity described in other estrogen target tissues. Estrogen-mediated reversal of antiestrogen suppression of DNA polymerase activity was paralleled by increases in total DNA synthesis.
D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005260:Female; D006801:Humans; D009256:Nafoxidine / Q000494:pharmacology
D004965:Estrogen Antagonists; D009256:Nafoxidine; D004958:Estradiol; D004259:DNA-Directed DNA Polymerase