Fanger B O, Currie R A, Cidlowski J A
Arch Biochem Biophys. 1986 Aug 15;249(1):116-25. doi: 10.1016/0003-9861(86)90566-7.
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.
糖皮质激素已被证明可通过依赖糖皮质激素受体的机制增加HeLa S3细胞中的表皮生长因子（EGF）受体。我们现在研究了同步化的HeLa S3细胞中表皮生长因子（EGF）受体的基础水平和糖皮质激素诱导水平，并将这些发现与糖皮质激素受体的核结合、受体激活以及糖皮质激素受体的几种物理化学性质相关联。细胞周期中EGF受体结合的定量分析表明，细胞周期中EGF受体数量没有显著变化。地塞米松处理非同步化的HeLa S3细胞会导致处理后48小时内EGF受体数量增加约131%。在细胞周期的G1/S晚期边界同步化的细胞中给予糖皮质激素，处理后8 - 9小时表皮生长因子受体数量增加约80%。随着细胞进入细胞周期的G2/M期和早期G1期，这种激素诱导的反应消失。相比之下，在G2/M期向同步化细胞给予激素，8或9小时后没有效果，但当这些细胞重新进入G1晚期时会出现反应。糖皮质激素无法诱导EGF受体结合与完整细胞在37℃时糖皮质激素受体的核转位以及体外通过升温将受体激活为DNA结合蛋白有关。通过羟基磷灰石层析分析发现，完整细胞中核受体结合的减少和体外受体激活的减弱与一种紧密结合的糖皮质激素受体形式的检测有关。这些分析表明，糖皮质激素在G2/M期和早期G1期未能诱导EGF受体结合可能是由于受体激活减少，这可能是糖皮质激素受体转录后修饰的结果。
