Moutsatsou Paraskevi, Papavassiliou Athanasios G
Department of Biological Chemistry, Medical School, University of Athens, Athens, Greece.
J Cell Mol Med. 2008 Jan-Feb;12(1):145-63. doi: 10.1111/j.1582-4934.2007.00177.x. Epub 2007 Dec 5.
Glucocorticoids are provided as co-medication with chemotherapy in breast cancer, albeit several lines of evidence indicate that their use may have diverse effects and in fact may inhibit chemosensitivity. The molecular basis of glucocorticoid-induced resistance to chemotherapy in breast cancer remains poorly defined. Recent researchers, in an attempt to clarify some aspects of the underlying pathways, provide convincing evidence that glucocorticoids induce effects that are dependent upon the glucocorticoid receptor -mediated transcriptional regulation of specific genes known to play key roles in cellular/tissue functions, including growth, apoptosis, differentiation, metastasis and cell survival. In this review, we focus on how glucocorticoid-induced chemoresistance in breast cancer is mediated by the glucocorticoid receptor, unraveling the molecular interplay of glucocorticoid receptor signaling with other signaling cascades prevalent in breast cancer. We also include a detailed description of glucocorticoid receptor structure and function, summarizing data gained during recent years into the mechanism(s) of the cross-talk between the glucocorticoid receptor and other signaling cascades and secondary messengers, via which glucocorticoids exert their pleiotropic effects.
糖皮质激素在乳腺癌化疗中作为辅助药物使用，尽管有多项证据表明其使用可能产生多种影响，实际上可能会抑制化疗敏感性。乳腺癌中糖皮质激素诱导化疗耐药的分子基础仍不清楚。最近的研究人员试图阐明潜在途径的某些方面，提供了令人信服的证据，表明糖皮质激素诱导的效应取决于糖皮质激素受体介导的特定基因的转录调控，这些基因在细胞/组织功能（包括生长、凋亡、分化、转移和细胞存活）中起关键作用。在这篇综述中，我们重点关注糖皮质激素受体如何介导乳腺癌中糖皮质激素诱导的化疗耐药性，揭示糖皮质激素受体信号与乳腺癌中普遍存在的其他信号级联之间的分子相互作用。我们还详细描述了糖皮质激素受体的结构和功能，总结了近年来关于糖皮质激素受体与其他信号级联和第二信使之间相互作用机制的数据，糖皮质激素通过这些机制发挥其多效性作用。
