Effect of low dose bisphenol A on the early differentiation of human embryonic stem cells into mammary epithelial cells
Effect of low dose bisphenol A on the early differentiation of human embryonic stem cells into mammary epithelial cells
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低剂量双酚A对人胚胎干细胞早期分化为乳腺上皮细胞的影响
DOI：
10.1016/j.toxlet.2013.01.026
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发表时间：
2013-04-26
影响因子：
3.5
通讯作者：
Zhuang, Zhixiong
中科院分区：
文献类型：
--
作者：
Yang, Linqing;Luo, Lingfeng;Zhuang, Zhixiong
先前已有报道称双酚A（BPA）会干扰实验动物乳腺结构的发育，并增加患乳腺癌的风险。在本研究中，应用人胚胎干细胞（hESC）分化为乳腺上皮细胞的体外模型来研究低剂量BPA对乳腺发生早期阶段的影响。通过一种成熟的三维（3D）培养系统将一个新建立的hESC系定向分化为乳腺上皮细胞。通过免疫荧光和蛋白质印迹分析对分化的乳腺上皮细胞进行鉴定，并根据这些数据将其称为诱导分化的乳腺上皮细胞（iDMECs）。在分化过程中，用10⁻⁹ - 10⁻⁶ M低剂量范围的BPA处理hESCs，以二甲基亚砜（DMSO）作为溶剂对照，以17 - β - 雌二醇（E2）作为雌激素阳性对照。我们的研究结果表明，低剂量BPA和E2能够影响iDMECs的乳腺球面积，并上调Oct4和Nanog蛋白的表达水平，而只有BPA能够下调E - 钙黏蛋白的表达。总之，本研究为低剂量BPA对乳腺上皮细胞早期分化阶段的影响提供了一些见解，并表明在早期分化阶段低剂量BPA的作用下iDMECs更易处于癌变状态。（c）2013爱思唯尔爱尔兰有限公司。保留所有权利。
It has been previously reported that Bisphenol A (BPA) can disturb the development of mammary structure and increase the risk of breast cancer in experimental animals. In this study, an in vitro model of human embryonic stem cell (hESC) differentiation into mammary epithelial cells was applied to investigate the effect of low dose BPA on the early stages of mammogenesis. A newly established hESC line was directionally differentiated into mammary epithelial cells by a well-established three-dimensional (3D) culture system. The differentiated mammary epithelial cells were characterized by immunofluorescence and western blotting assay, and were called induced differentiated mammary epithelial cells (iDMECs) based on these data. The hESCs were treated with low doses of BPA range 10(-9)-10(-6) M during the differentiation process, with DMSO as the solvent control and 17-beta-estrodiol (E2) as the estrogen-positive control. Our results showed that low dose BPA and E2 could influence the mammosphere area of iDMECs and upregulate the expression level of Oct4 and Nanog proteins, while only BPA could downregulate the expression of E-cadherin protein. Taken together, this study provides some insights into the effects of low dose BPA on the early differentiation stage of mammary epithelial cells and suggests an easier canceration status of iDMECs under the effect of low dose BPA during its early differentiation stage. (c) 2013 Elsevier Ireland Ltd. All rights reserved.