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17β-Estradiol via Orai1 activates calcium mobilization to induce cell proliferation in epithelial ovarian cancer.
Journal of Biochemical and Molecular Toxicology ( IF 3.6 ) Pub Date : 2020-08-25 , DOI: 10.1002/jbt.22603
Xiaoyu Lv 1 , Chunlei Miao 1 , Mengyan Liu 1 , Xinbo Wang 2 , Lin Wang 3 , Di Wang 1
Affiliation  

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 Ca2+ 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.

中文翻译:

经由Orai1的17β-雌二醇激活钙动员,诱导上皮性卵巢癌细胞增殖。

上皮性卵巢癌(EOC)是最致命的雌激素敏感性妇科癌症。研究报告说,雌激素可诱导细胞中快速的细胞钙动员,并可决定细胞的命运。我们发现雌激素增加了SK-OV-3细胞中钙释放激活的钙通道调节剂1(Orai1)的蛋白表达水平。然而,迄今为止,尚未有关于在EOC发育过程中调节雌激素Orai1的功能关系和分子机制的研究。在我们的研究中,Orai1在高度浆液性卵巢肿瘤组织和SK-OV-3细胞中具有高表达水平。雌激素促进细胞增殖和迁移,同时抑制SK-OV-3细胞的细胞凋亡。Orai1沉默抑制雌激素诱导的细胞迁移和增殖。但是,Orai1的过表达 增强了17β-雌二醇(E2)发挥其功能的能力。雌激素诱导SK‐OV‐3细胞中钙快速流入。敲除SK‐OV‐3细胞中的Orai1可以阻断E2诱导的存储操作的Ca2+涌入。在E2处理下,通过Orai1调节caspase 3,基质金属肽酶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诱导钙内流以确定细胞命运。
更新日期:2020-08-25
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