title: Regulation of epidermal growth factor receptors by glucocorticoids during the cell cycle in HeLa S3 cells.
abstract: Glucocorticoids have been shown to increase epidermal growth factor (EGF) receptors in HeLa S3 cells via mechanisms dependent upon glucocorticoid receptors. We have now examined the basal and glucocorticoid-induced levels of epidermal growth factor (EGF) receptors in synchronized HeLa S3 cells and related these findings to glucocorticoid receptor nuclear binding, receptor activation, and several physiochemical properties of the glucocorticoid receptor. Quantitation of EGF receptor binding during the cell cycle indicates that no significant variation in EGF receptor number occurs during the cell cycle. Dexamethasone treatment of nonsynchronized HeLa S3 cells results in an approximately 131% increase in EGF receptor number within 48 h of treatment. Administration of glucocorticoids to cells synchronized at the late G1/S phase boundary of the cell cycle results in an approximately 80% increase in epidermal growth factor receptors 8-9 h after treatment. This hormone-induced response disappears as cells enter the G2/M and early G1 phases of the cell cycle. In contrast, hormone administration to synchronized cells during the G2/M phases is without effect after 8 or 9 h, but a response is evident when these cells reenter the late G1 phase. This inability of glucocorticoids to induce EGF receptor binding has been correlated with nuclear glucocorticoid receptor translocation at 37 degrees C in intact cells and activation of receptors in vitro to DNA binding proteins by warming. This reduction in nuclear receptor binding in intact cells and diminished in vitro activation of receptor are associated with the detection of a tightly binding glucocorticoid receptor form as analyzed by hydroxylapatite chromatography. These analyses suggest that the failure of glucocorticoids to induce EGF receptor binding during the G2/M and early G1 phases may be the result of decreased receptor activation which may result from a post-transcriptional modification of the glucocorticoid receptor.
mesh_terms: D002453:Cell Cycle; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D004815:Epidermal Growth Factor / Q000378:metabolism*; D066246:ErbB Receptors; D006367:HeLa Cells; D006358:Hot Temperature; D006801:Humans; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D011956:Receptors, Cell Surface; D011965:Receptors, Glucocorticoid; D004815:Epidermal Growth Factor; D003907:Dexamethasone; D066246:ErbB Receptors