Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Via Pietro Bucci, Arcavacata di Rende, 87036 Cosenza, Italy.
Int J Mol Sci. 2022 Jan 22;23(3):1242. doi: 10.3390/ijms23031242.
It is known that estrogen stimulates growth and inhibits apoptosis through estrogen receptor(ER)-mediated mechanisms in many cancer cell types. Interestingly, there is strong evidence that estrogens can also induce apoptosis, activating different ER isoforms in cancer cells. It has been observed that E2/ERα complex activates multiple pathways involved in both cell cycle progression and apoptotic cascade prevention, while E2/ERβ complex in many cases directs the cells to apoptosis. However, the exact mechanism of estrogen-induced tumor regression is not completely known. Nevertheless, ERs expression levels of specific splice variants and their cellular localization differentially affect outcome of estrogen-dependent tumors. The goal of this review is to provide a general overview of current knowledge on ERs-mediated apoptosis that occurs in main hormone dependent-cancers. Understanding the molecular mechanisms underlying the induction of ER-mediated cell death will be useful for the development of specific ligands capable of triggering apoptosis to counteract estrogen-dependent tumor growth.
已知雌激素通过许多癌细胞类型中的雌激素受体（ER）介导的机制刺激生长并抑制细胞凋亡。有趣的是，有强有力的证据表明雌激素也可以诱导细胞凋亡，在癌细胞中激活不同的 ER 同工型。已经观察到 E2/ERα 复合物激活涉及细胞周期进展和凋亡级联预防的多个途径，而 E2/ERβ 复合物在许多情况下指导细胞凋亡。然而，雌激素诱导肿瘤消退的确切机制尚不完全清楚。尽管如此，特定剪接变体的 ERs 表达水平及其细胞定位差异会影响雌激素依赖性肿瘤的结局。本综述的目的是提供关于主要激素依赖性癌症中发生的 ER 介导的细胞凋亡的现有知识的概述。了解诱导 ER 介导的细胞死亡的分子机制对于开发能够触发凋亡以对抗雌激素依赖性肿瘤生长的特异性配体将是有用的。
