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Potential interference of aluminum chlorohydrate with estrogen receptor signaling in breast cancer cells

机译：氯化铝对乳腺癌细胞中雌激素受体信号的潜在干扰

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Aluminum salts are widely used as the active antiperspirant in underarm cosmetic. Experimental observations indicate that its long term application may correlate with breast cancer development and progression. This action is proposed to be attributed, among others, to aluminum possible estrogen-like activities. In this study we showed that aluminum, in the form of aluminum chlorohydrate (ACH), caused increase in estrogen receptor alpha (ERα) protein levels, in ERα-positive MCF-7 cells. This effect was accompanied by moderate activation of Estrogen Response Elements (ERE)-driven reporter gene expression and 20%-50% increase in certain estrogen responsive, ERE-independent genes expression. Genes affected were ERα, p53, cyclin D1, and c-fos, crucial regulators of breast cancer development and progression. ACH-induced genes expression was eliminated in the presence of the estrogen antagonist: ICI 182780, in MCF-7 cells, whereas it was not observed in ERα-negative MDA-MB-231 breast cancer cells, indicating aluminum interference with estrogen signaling. Moreover, ACH caused increase in the perinuclear localization of estrogen receptor alpha in MCF-7 breast cancer cells and increase in the mitochondrial Bcl-2 protein, possibly affecting receptors-mediated mitochondrial actions and mitochondrial-dependent apoptosis. ACH-induced perinuclear localization of estrogen receptor beta was also observed in MDA-MB-231. Our findings indicate that aluminum actions on estrogen receptors protein level and subcellular localization possibly affect receptors-mediated actions and thus, aluminum interference with estrogen signaling.
机译：铝盐被广泛用作腋下化妆品中的活性止汗剂。实验观察表明，其长期应用可能与乳腺癌的发生和发展有关。提议将该作用归因于铝可能的类似雌激素的活性。在这项研究中，我们发现铝以氯水合铝（ACH）的形式引起了ERα阳性MCF-7细胞中雌激素受体α（ERα）蛋白质水平的增加。此作用伴随有适度激活雌激素反应元件（ERE）驱动的报告基因表达，某些雌激素反应性，ERE独立基因表达增加20％-50％。受影响的基因是ERα，p53，细胞周期蛋白D1和c-fos，它们是乳腺癌发展和进程的关键调节因子。在雌激素拮抗剂：ICI 182780的存在下，ACH诱导的基因表达在MCF-7细胞中被消除，而在ERα阴性的MDA-MB-231乳腺癌细胞中未观察到，表明铝干扰了雌激素信号传导。此外，ACH导致MCF-7乳腺癌细胞中雌激素受体α的核周定位增加以及线粒体Bcl-2蛋白增加，可能影响受体介导的线粒体作用和线粒体依赖性细胞凋亡。在MDA-MB-231中也观察到ACH诱导的雌激素受体β的核周定位。我们的发现表明，铝对雌激素受体蛋白质水平和亚细胞定位的作用可能影响受体介导的作用，因此，铝对雌激素信号的干扰。

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