Effects of bisphenol A exposure on the proliferation and senescence of normal human mammary epithelial cells
Effects of bisphenol A exposure on the proliferation and senescence of normal human mammary epithelial cells
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DOI：
10.4161/cbt.18942
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发表时间：
2012-03-01
影响因子：
3.6
通讯作者：
Sone, Hideko
中科院分区：
文献类型：
--
作者：
Qin, Xian-Yang;Fukuda, Tomokazu;Sone, Hideko
双酚A （BPA）的致癌活性刺激了雌激素依赖性乳腺癌组织、细胞系和啮齿动物的生长。然而，目前还不完全清楚这种化合物是如何促进乳腺癌发生的。在我们的研究中，我们研究了BPA对人乳腺上皮细胞（HMEC）细胞增殖和衰老的影响。在传代第8代早期暴露于BPA 1周后，HMEC在传代第16代后期的增殖和球体大小均增加，提示BPA具有调节乳腺上皮细胞生长的能力。有趣的是，人类异染色质蛋白-1的数量。在bpa处理的细胞中，作为衰老标志的阳性细胞也有所增加。与这些发现一致的是，p16和cyclin E的蛋白水平在bpa暴露的HMEC中升高，这两种蛋白水平分别诱导细胞衰老和促进细胞增殖。此外，在bpa暴露的HMEC中，与大多数或所有肿瘤类型发展相关的基因（如BRCA1、CCNA1、CDKN2A （p16）、THBS1、TNFRSF10C和TNFRSF10D）的DNA甲基化水平升高。我们在HMEC模型中的研究结果表明，BPA的遗传和表观遗传改变可能损害HMEC功能，导致与细胞增殖和衰老相关的复杂活动，在乳腺癌发生中发挥作用。这份手稿在印刷前已在网上发表。一旦问题完成并分配了页码，引用将相应更改。
The carcinogenic activity of bisphenol A (BPA) is responsible for stimulating growth in estrogen-dependent breast cancer tissues, cell lines and rodent studies. However, it is not fully understood how this compound promotes mammary carcinogenesis. In our study, we examined the effect of BPA on cellular proliferation and senescence in human mammary epithelial cells (HMEC). Exposure to BPA for 1 week at the early stage at passage 8 increased the proliferation and sphere size of HMEC at the later stage up to passage 16, suggesting that BPA has the capability to modulate cell growth in breast epithelial cells. Interestingly, the number of human heterochromatin protein-1. positive cells, which is a marker of senescence, was also increased among BPA-treated cells. Consistent with these findings, the protein levels of both p16 and cyclin E, which are known to induce cellular senescence and promote proliferation, respectively, were increased in BPA-exposed HMEC. Furthermore, DNA methylation levels of genes related to development of most or all tumor types, such as BRCA1, CCNA1, CDKN2A (p16), THBS1, TNFRSF10C and TNFRSF10D, were increased in BPA-exposed HMEC. Our findings in the HMEC model suggested that the genetic and epigenetic alterations by BPA might damage HMEC function and result in complex activities related to cell proliferation and senescence, playing a role in mammary carcinogenesis. This manuscript has been published online, prior to printing. Once the issue is complete and page numbers have been assigned, the citation will change accordingly.