Molecular mechanisms regulating glucocorticoid sensitivity and resistance.

Molecular mechanisms regulating glucocorticoid sensitivity and resistance.
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DOI:
10.1016/j.mce.2008.10.001
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发表时间:
2009-03-05
影响因子:
4.1
通讯作者:
Cidlowski JA
Cidlowski JA
中科院分区:
医学2区
文献类型:
--
作者:
Gross KL;Lu NZ;Cidlowski JA

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糖皮质激素受体激动剂是治疗各种血液系统恶性肿瘤的主要药物。糖皮质激素因其刺激细胞内信号转导级联的能力而被包括在治疗方案中,所述细胞内信号转导级联最终导致参与细胞周期进展和程序性细胞死亡的基因的转录速率的改变。不幸的是,接受全身糖皮质激素治疗这些疾病的患者亚群对糖皮质激素诱导的细胞死亡不敏感或变得不敏感,这种现象被认为是糖皮质激素抵抗。已经确定了导致糖皮质激素抵抗的多种因素。在这里,我们总结了这些机制中的几个,并描述了从一个基因产生一个主机的糖皮质激素受体亚型的过程。糖皮质激素受体亚型在决定细胞对糖皮质激素的反应性的潜在作用被强调。
Glucocorticoid receptor agonists are mainstays in the treatment of various malignancies of hematological origin. Glucocorticoids are included in therapeutic regimens for their ability to stimulate intracellular signal transduction cascades that culminate in alterations in the rate of transcription of genes involved in cell cycle progression and programmed cell death. Unfortunately, subpopulations of patients undergoing systemic glucocorticoid therapy for these diseases are or become insensitive to glucocorticoid-induced cell death, a phenomenon recognized as glucocorticoid resistance. Multiple factors contributing to glucocorticoid resistance have been identified. Here we summarize several of these mechanisms and describe the processes involved in generating a host of glucocorticoid receptor isoforms from one gene. The potential role of glucocorticoid receptor isoforms in determining cellular responsiveness to glucocorticoids is emphasized.
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发表时间: 1994-12-01
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