Altered Glucocorticoid Binding and Action in Response to Epidermal Growth Factor in HBL100 Cells1

Incubation of adherent human breast epithelial HBL100 cells with epidermal growth factor (EGF) decreased [3H]dexamethasone binding by 35% with no effect on affinity. Maximal inhibition was obtained at 3 n\i EGF and the 50% effective dose was 0.2 mi EGF. Decreased dexamethasone binding induced by 3 n\i EGF was maximal by 5 min of treatment and, in the continuous presence of EGF, persisted at a constant level over 4 days. The action of EGF was antagonized by 12-O-tetradecanoylphorbol-13-acetate, which did not inhibit dexamethasone binding significantly, and by concanavalin A. In homogenates of EGF-treated cells, decreased dexamethasone binding was observed only in the cytosolic fraction. Saturation dexamethasone binding inhibited the growth rate of 11HI 100 cells by approximately 50%, but concurrent treatment with EGF over came this inhibition. The effect of EGF on dexamethasone-inhibited cell growth also was antagonized by 12-O-tetradecanoylphorbol-13-acetate.