REGULATION OF EPIDERMAL GROWTH-FACTOR RECEPTORS BY GLUCOCORTICOIDS DURING THE CELL-CYCLE IN HELA S3 CELLS
REGULATION OF EPIDERMAL GROWTH-FACTOR RECEPTORS BY GLUCOCORTICOIDS DURING THE CELL-CYCLE IN HELA S3 CELLS
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DOI：
10.1016/0003-9861(86)90566-7
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发表时间：
1986-08-15
影响因子：
3.9
通讯作者：
CIDLOWSKI, JA
中科院分区：
文献类型：
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作者：
FANGER, BO;CURRIE, RA;CIDLOWSKI, JA
糖皮质激素已被证明可以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。我们现在检查了同步 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核结合、受体激活和糖皮质激素受体的几种理化特性相关联。细胞周期期间 EGF 受体结合的定量表明，细胞周期期间 EGF 受体数量没有发生显着变化。地塞米松处理不同步的 HeLa S3 细胞会产生约 .治疗 48 小时内 EGF 受体数量增加 131%。对在细胞周期的晚期G1/S期边界同步的细胞施用糖皮质激素导致.apprx。治疗后8-9小时表皮生长因子受体增加80%。当细胞进入细胞周期的 G2/M 期和早期 G1 期时，这种激素诱导的反应就会消失。相比之下，在 G2/M 期期间对同步细胞施用激素在 8 或 9 小时后没有效果，但当这些细胞重新进入 G1 期晚期时，反应很明显。糖皮质激素不能诱导EGF受体结合与37°核糖皮质激素受体易位相关。 C 完整细胞中的 C 以及通过加热在体外激活 DNA 结合蛋白的受体。完整细胞中核受体结合的减少和受体体外激活的减少与通过羟磷灰石色谱法分析的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糖皮质激素受体转录后修饰导致激活减少的结果。
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 physicochemical 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 .apprx. 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 .apprx. 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 .degree. 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 activation which may result from a post-transcriptional modification of the glucocorticoid receptor.