尽管进行了广泛的研究，但负责雌激素生理作用的基因/蛋白质和途径仍然难以捉摸。在这项研究中，我们使用蛋白质组学方法确定了雌激素对乳腺癌 MCF7 细胞总体蛋白质表达的影响。 17-β-雌二醇 (E2) 显着改变了 77 种胞浆蛋白、74 种核蛋白和 81 种膜/细胞器蛋白的表达。蛋白质富集分析表明，E2 可能主要通过促进 G1 到 S 相转变和推进 G2/M 检查点来刺激细胞分裂。 E2对细胞存活的影响是复杂的，因为它可以同时增强和抑制细胞凋亡。生物信息学分析提示，E2可能通过促进线粒体中成孔蛋白Bax的积累来增强细胞凋亡，并通过激活PI3K/AKT/mTOR信号通路抑制细胞凋亡。我们使用免疫印迹验证了 PI3K 信号传导的激活以及 E2 处理的细胞膜/细胞器部分中 Bax 的积累。与单独用E2处理的细胞相比，用E2和PI3K抑制剂Ly294002处理MCF7细胞显着增强细胞凋亡，这表明雌激素与PI3K抑制剂联合可能是治疗ERα阳性乳腺癌的有前途的策略。有趣的是，许多 E2 上调蛋白含有 HEAT、KH 和 RRM 结构域。

Despite extensive research, the genes/proteins and pathways responsible for the physiological effects of estrogen remain elusive. In this study, we determined the effect of estrogen on global protein expression in breast cancer MCF7 cells using a proteomic method. The expression of 77 cytosolic, 74 nuclear, and 81 membrane/organelle proteins was significantly altered by 17-β-estradiol (E2). Protein enrichment analyses suggest that E2 may stimulate cell division primarily by promoting the G1 to S phase transition and advancing the G2/M checkpoint. The effect of E2 on cell survival was complex, as it could simultaneously enhance and inhibit apoptosis. Bioinformatics analysis suggests that E2 may enhance apoptosis by promoting the accumulation of the pore-forming protein Bax in the mitochondria and inhibit apoptosis by activating the PI3K/AKT/mTOR signaling pathway. We verified the activation of the PI3K signaling and the accumulation of Bax in the membrane/organelle fraction in E2-treated cells using immunoblotting. Treatment of MCF7 cells with E2 and the PI3K inhibitor Ly294002 significantly enhanced apoptosis compared to those treated with E2 alone, suggesting that combining estrogen with a PI3K inhibitor could be a promising strategy for treating ERα-positive breast cancer. Interestingly, many of the E2-upregulated proteins contained the HEAT, KH, and RRM domains.