The effects of estrogens and antiestrogens on hormone-responsive human breast cancer in long-term tissue culture.
We have established or characterized six lines of human breast cancer maintained in long-term tissue culture for at least 1 year and have examined these lines for estrogen responsiveness. One of these cell lines, MCF-7, shows marked stimulation of macromolecular synthesis and cell division with physiological concentrations of estradiol. Antiestrogens are strongly inhibitory, and at concentrations greater than 3 X 10(-7) M they kill cells. Antiestrogen effects are prevented by simultaneous treatment with estradiol or reversed by addition of estradiol to cells incubated in antiestrogen. Responsive cell lines contain high-affinity specific estradiol receptors. Antiestrogens compete with estradiol for these receptors but have a lower apparent affinity for the receptor than estrogens. Stimulation of cells by estrogens is biphasic, with inhibition and cell death at concentrations of 17beta-estradiol or diethylstilbestrol exceeding 10(-7) M. Killing by high concentrations of estrogen is probably a nonspecific effect in that we observe this response with 17alpha-estradiol at equivalent concentrations and in the otherwise unresponsive cells that contain no estrogen receptor sites.
D001665:Binding Sites; D001667:Binding, Competitive; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004054:Diethylstilbestrol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology; D004965:Estrogen Antagonists; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D006801:Humans; D009594:Nitromifene / Q000494:pharmacology; D012334:RNA, Neoplasm / Q000096:biosynthesis; D011960:Receptors, Estrogen; D013629:Tamoxifen / Q000494:pharmacology
D004273:DNA, Neoplasm; D004965:Estrogen Antagonists; D004967:Estrogens; D012334:RNA, Neoplasm; D011960:Receptors, Estrogen; D013629:Tamoxifen; D004958:Estradiol; D009594:Nitromifene; D004054:Diethylstilbestrol