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双酚A暴露通过雌激素受体介导的整合素β1/基质金属蛋白酶-9途径促进NCM460细胞迁移。

Bisphenol a exposure promotes the migration of NCM460 cells via estrogen receptor-mediated integrin β1/MMP-9 pathway.

作者信息

Shi Tonglin, Zhao Chao, Li Zhuoyu, Zhang Quanbin, Jin Xiaoting

机构信息

Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Biotechnology, Shanxi University, Taiyuan, Shanxi, 030006, People's Republic of China.

Central Laboratory of Taiyuan Central Hospital, No. 1, East Sandao Alley, Xinghualing District, Taiyuan, Shanxi, 030009, People's Republic of China.

出版信息

Environ Toxicol. 2016 Jul;31(7):799-807. doi: 10.1002/tox.22090. Epub 2014 Dec 23.

DOI:10.1002/tox.22090
PMID:25534675
Abstract

Bisphenol A (BPA) is a widely used industrial chemical and also an environmental endocrine disruptor (EED), which serves as a monomer in the manufacture of polycarbonate plastics. BPA enters human body mainly through oral intake, and has been reported as being linked to oncogenesis in many tissues. However, the association of BPA intake with gastrointestinal cancer, such as colon cancer, has received less attention. The present study was conducted to investigate the effects of BPA on the migration of normal colon epithelial cells (NCM460 cells) and further elucidate the underlying mechanisms. Our data showed that 1 × 10(-8) M (equivalent to environmental concentration) of BPA potently promoted the migration of NCM460 cells. Interestingly, BPA treatment induced an increase of integrin β1 expression, and the functional blocking of integrin β1 abolished the migration-promoting effects of BPA. Moreover, the results showed that it was estrogen receptor β but not estrogen receptor α that was involved in this migration promotion. In addition, cellular exposure of BPA stimulated the expression and activity of MMP-9, a well-known factor of cell migration. Taken together, these results indicate that environmental concentration of BPA exposure promotes cell migration through activating ERβ-mediated integrin β1/MMP-9 pathway, suggesting exposure to BPA in the colon may present a potential cancer risk. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 799-807, 2016.

摘要

双酚A(BPA)是一种广泛使用的工业化学品,也是一种环境内分泌干扰物(EED),它在聚碳酸酯塑料制造中作为单体。双酚A主要通过口服进入人体,并且已有报道称其与许多组织的肿瘤发生有关。然而,双酚A摄入量与胃肠道癌症(如结肠癌)之间的关联较少受到关注。本研究旨在调查双酚A对正常结肠上皮细胞(NCM460细胞)迁移的影响,并进一步阐明其潜在机制。我们的数据表明,1×10(-8)M(相当于环境浓度)的双酚A能显著促进NCM460细胞的迁移。有趣的是,双酚A处理导致整合素β1表达增加,并且整合素β1的功能阻断消除了双酚A的迁移促进作用。此外,结果表明参与这种迁移促进作用的是雌激素受体β而不是雌激素受体α。另外,双酚A的细胞暴露刺激了MMP - 9(一种众所周知的细胞迁移因子)的表达和活性。综上所述,这些结果表明环境浓度的双酚A暴露通过激活ERβ介导的整合素β1/MMP - 9途径促进细胞迁移,提示结肠中暴露于双酚A可能存在潜在的癌症风险。©2014威利期刊公司。《环境毒理学》31: 799 - 807,2016年。

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