EFFECTS OF GLUCOCORTICOIDS AND PROGESTERONE ON HORMONE-RESPONSIVE HUMAN BREAST-CANCER IN LONG-TERM TISSUE-CULTURE

Abstract

Glucocorticoids [dexamethasone and cortisol] at physiological concentration, inhibit cell division and thymidine incorporation in 3 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 h after hormone addition. All 3 of these lines have glucocorticoid receptors demonstrable by competitive protein binding assays. Receptors are extensively characterized in 1 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 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. In some cases glucocorticoids can directly limit growth in human breast cancer in vitro without requiring alterations in other tropic hormones.