The effects of glucocorticoids and progesterone on hormone-responsive human breast cancer in long-term tissue culture.
Glucocorticoids, at physiological concentration, inhibit cell division and thymidine incorporation in three lines of human breast cancer maintained in long-term tissue culture. At steroid concentrations sufficient to inhibit thymidine incorporation 50%, little or no effect is seen on protein synthesis 48 hr after hormone addition. All three of these lines are shown to have glucocorticoid receptors demonstrable by competitive protein binding assays. Receptors are extensively characterized in one line by sucrose density gradient analysis and binding specificity studies. Good correlation between receptor-binding specificity and biological activity is found except for progesterone, which binds to glucocorticoid receptor but is noninhibitory. Cross-competition and quantification studies demonstrate a separate receptor for progesterone. This receptor has limited binding specificities restricted largely to progestational agents, whereas the glucocorticoid receptor bound both glucocorticoids and progesterone. Two other human breast cancer lines neither contain glucocorticoid receptor nor are inhibited by glucocorticoids. It is concluded that in some cases glucocorticoids can directly limit growth in human breast cancer in vitro without requiring alterations in other trophic hormones.
D001665:Binding Sites; D001667:Binding, Competitive; D001943:Breast Neoplasms / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D004273:DNA, Neoplasm / Q000096:biosynthesis; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D007700:Kinetics; D011374:Progesterone / Q000494:pharmacology*; D011965:Receptors, Glucocorticoid; D011980:Receptors, Progesterone; D011987:Receptors, Steroid
D004273:DNA, Neoplasm; D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D011980:Receptors, Progesterone; D011987:Receptors, Steroid; D011374:Progesterone; D003907:Dexamethasone; D006854:Hydrocortisone