Singh Rajesh R, Kumar Rakesh
The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
J Cell Biochem. 2005 Oct 15;96(3):490-505. doi: 10.1002/jcb.20566.
Excessive activation of the hormone signaling pathways is implicated in several disorders of the target tissues, with cancer being one of the most serious fallouts. Steroid hormone receptors are key proteins through which steroid hormones convey their signals to the cells. Deregulated activity of the hormone receptors due to their altered activation; stability or sub-cellular localization is heavily implicated in the onset and progress of cancers. The role played by estrogen and its receptors in breast cancer remains the most thoroughly investigated steroid-dependent cancer system till date. Choosing it as an example, we have summarized the molecular mechanisms underlying the action of the estrogen receptors (ERs) in manifesting the effects of the estrogens in the cells. A special emphasis is placed on the molecular mechanism of their functionality, role of the coactivator proteins, and the reasons for the deregulated signaling. The therapeutic approaches resulting from the mechanistic study of the ER action and their efficacies are also discussed.
激素信号通路的过度激活与多种靶组织疾病有关，癌症是其中最严重的后果之一。类固醇激素受体是类固醇激素将信号传递给细胞的关键蛋白。由于激素受体的激活、稳定性或亚细胞定位发生改变而导致的活性失调，与癌症的发生和发展密切相关。雌激素及其受体在乳腺癌中所起的作用，至今仍是研究最为深入的类固醇依赖性癌症系统。以其为例，我们总结了雌激素受体（ERs）在细胞中发挥雌激素作用的分子机制。特别强调了其功能的分子机制、共激活蛋白的作用以及信号失调的原因。还讨论了基于ER作用机制研究的治疗方法及其疗效。
