Plastic Surgery Institute, Weifang Medical University, Weifang, Shandong, China.
Department of Gynecology, Affiliated Hospital of Weifang Medical University, Weifang, Shandong, China.
J Biochem Mol Toxicol. 2020 Dec;34(12):e22603. doi: 10.1002/jbt.22603. Epub 2020 Aug 25.
Epithelial ovarian cancer (EOC) is the most lethal estrogen-sensitive gynecological cancer. Studies have reported that estrogen induces rapid cellular calcium mobilization in cells and can determine the fate of a cell. We found that estrogen increased the calcium release-activated calcium channel modulator 1 (Orai1) protein expression levels in SK-OV-3 cells. However, to date, there has been no research on the functional relationship and molecular mechanism of estrogen-regulating Orai1 during EOC development. In our study, Orai1 had a high expression level in high-grade serous ovarian tumor tissues and SK-OV-3 cells. Estrogen promoted cell proliferation and migration while inhibiting cell apoptosis in SK-OV-3 cells. Orai1 silencing suppressed estrogen-induced cell migration and proliferation. Overexpression of Orai1, however, enhanced the ability of 17β-estradiol (E2) to exert its function. Estrogen induced rapid calcium influx in SK-OV-3 cells. Knockdown of Orai1 in SK-OV-3 cells blocked E2-induced stored-operated Ca influx. The messenger RNA expression of caspase 3, matrix metallopeptidase 1, and cyclin-dependent kinase 6 were regulated via Orai1 under E2 treatment. Our results suggest that estrogen, by regulating Orai1, induced calcium influx to determine cell fate.
上皮性卵巢癌 (EOC) 是最致命的雌激素敏感型妇科癌症。研究报道雌激素可在细胞中诱导快速的细胞钙动员，并能决定细胞的命运。我们发现，雌激素可增加 SK-OV-3 细胞中钙释放激活钙通道调制器 1 (Orai1) 蛋白的表达水平。然而，迄今为止，尚未有研究探讨雌激素在 EOC 发展过程中调节 Orai1 的功能关系和分子机制。在我们的研究中，Orai1 在高级别浆液性卵巢肿瘤组织和 SK-OV-3 细胞中高表达。雌激素促进 SK-OV-3 细胞的增殖和迁移，同时抑制细胞凋亡。Orai1 沉默抑制了雌激素诱导的细胞迁移和增殖。然而，Orai1 的过表达增强了 17β-雌二醇 (E2) 的作用能力。雌激素诱导 SK-OV-3 细胞中的快速钙内流。SK-OV-3 细胞中 Orai1 的敲低阻断了 E2 诱导的储存操纵钙内流。在 E2 处理下，Orai1 调节了 caspase 3、基质金属蛋白酶 1 和细胞周期蛋白依赖性激酶 6 的信使 RNA 表达。我们的结果表明，雌激素通过调节 Orai1 诱导钙内流来决定细胞命运。
