An unexpected effect of glucocorticoids on stimulation of c-fms proto-oncogene expression in choriocarcinoma cells that express little glucocorticoid receptor
An unexpected effect of glucocorticoids on stimulation of c-fms proto-oncogene expression in choriocarcinoma cells that express little glucocorticoid receptor
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DOI：
10.1016/j.ajog.2004.01.021
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发表时间：
2004-04-01
影响因子：
9.8
通讯作者：
Hochberg, RB
中科院分区：
文献类型：
--
作者：
Chambers, SK;Ivins, CM;Hochberg, RB
目的：本研究的目的是确定糖皮质激素刺激 JAR 绒毛膜癌细胞中 c-fms 原癌基因表达的机制，据报道，JAR 绒毛膜癌细胞缺乏糖皮质激素受体。研究设计：使用配体结合测定、Northern 和 Western 印迹、免疫组织化学、定量逆转录酶聚合酶链反应和核流失来测试糖皮质激素对 c-finis 的作用。实验结果：地塞米松以特定方式刺激JAR细胞中的c-fms (EC50 = 1 nmol/L)。 RU 486 和放线菌素 D 均抑制地塞米松刺激，这表明受体介导和转录调节作用。胞质或全细胞结合测定和免疫组织化学均未检测到 JAR 细胞中的糖皮质激素受体。然而，逆转录酶-聚合酶链式反应产物的 Southern blot 分析显示，JAR 细胞中糖皮质激素受体信使 RNA 的水平比 HeLa 对照细胞低约 100 倍。在所测试的几个 JAR 克隆中，除 1 个克隆之外的所有克隆中，糖皮质激素受体信使 RNA 的存在与否与糖皮质激素敏感性之间存在一致性。 结论：一些 JAR 细胞含有低水平的糖皮质激素受体，介导地塞米松刺激 c-fms 表达。这种对循环糖皮质激素的敏感性通过刺激 c-fms 相关的侵袭行为（这是绒毛膜癌的特征），赋予这些细胞生存优势。 (C) 2004 Elsevier Inc. 保留所有权利。
Objective: The purpose of this study was to determine the mechanism by which glucocorticoids stimulate c-fms proto-oncogene expression in JAR choriocarcinoma cells, which are reported to lack the glucocorticoid receptor.Study design: Glucocorticoid action on c-finis was tested with the use of ligand binding assays, Northern and Western blotting, immunohistochemistry, quantitative reverse transcriptase-polymerase chain reaction, and nuclear run-off experiments.Results: Dexamethasone stimulated c-fms (EC50 = 1 nmol/L) in JAR cells in a specific manner. Both RU 486 and actinomycin D inhibited dexamethasone stimulation, which suggests receptor-mediated and transcriptionally regulated actions. Neither cytosol or whole cell binding assays nor immunohistochemistry detected glucocorticoid receptor in JAR cells. However, Southern blot analysis of reverse transcriptase-polymerase chain reaction products revealed levels of glucocorticoid receptor messenger RNA in JAR cells that were approximately 100-fold lower than in HeLa control cells. In all but 1 clone among several JAR clones that were tested, there was concordance between presence or absence of glucocorticoid receptor messenger RNA and glucocorticoid sensitivity.Conclusion: Some JAR cells contain low levels of glucocorticoid receptor, which mediate dexamethasone stimulation of c-fms expression. Such sensitivity to circulating glucocorticoids confers a survival advantage to these cells by stimulating the c-fms-related invasive behavior so characteristic of choriocarcinomas. (C) 2004 Elsevier Inc. All rights reserved.