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

Department of Microbiology and Molecular Biology Institute, University of California at Los Angeles, Los Angeles, California 90024-1489

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 nM EGF and the 50% effective dose was 0.2 nM EGF. Decreased dexamethasone binding induced by 3 nM 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 HBL100 cells by approximately 50%, but concurrent treatment with EGF overcame this inhibition. The effect of EGF on dexamethasone-inhibited cell growth also was antagonized by 12-O-tetradecanoylphorbol-13-acetate.

¹ This work was supported by USPHS Grant AM25826.

² To whom requests for reprints should be addressed.

Received 5/12/87. Revised 8/ 7/87. Accepted 8/14/87.