Castillo Sanchez Rocio, Gomez Rocio, Perez Salazar Eduardo
Departamento de Toxicologia, ‡Departamento de Biologia Celular, Cinvestav-IPN , Mexico D.F., Mexico.
Chem Res Toxicol. 2016 Mar 21;29(3):285-95. doi: 10.1021/acs.chemrestox.5b00457. Epub 2016 Mar 7.
Bisphenol A (BPA) is an industrial synthetic chemical utilized in the production of numerous products including food and beverage containers. Humans are exposed to BPA during ingestion of contaminated water and food because it can leach from polycarbonate containers, beverage cans, and epoxy resins. BPA has been related with the development of several diseases including breast cancer. However, the signal transduction pathways mediated by BPA and its role as a promoter of migration and invasion in breast cancer cells remain to be investigated. Here, we demonstrate that BPA promotes migration, invasion, and an increase in the number of focal contacts in MDA-MB-231 breast cancer cells. Moreover, MDA-MB-231 cells express GPER, and BPA promotes migration through a GPER-dependent pathway. BPA also induces activation of FAK, Src, and ERK2, whereas migration induced by BPA requires the activity of these kinases. In addition, BPA induces an increase on AP-1- and NFκB-DNA binding activity through an Src- and ERK2-dependent pathway. In conclusion, our findings demonstrate, that BPA induces the activation of signal transduction pathways, which mediate migration, AP-1/NFκB-DNA binding activity, and an invasion process in MDA-MB-231 breast cancer cells.
双酚A(BPA)是一种工业合成化学物质,用于生产包括食品和饮料容器在内的众多产品。人类在摄入受污染的水和食物时会接触到双酚A,因为它会从聚碳酸酯容器、饮料罐和环氧树脂中渗出。双酚A与包括乳腺癌在内的多种疾病的发生有关。然而,双酚A介导的信号转导途径及其在乳腺癌细胞迁移和侵袭中作为促进剂的作用仍有待研究。在此,我们证明双酚A促进MDA-MB-231乳腺癌细胞的迁移、侵袭以及粘着斑数量的增加。此外,MDA-MB-231细胞表达G蛋白偶联雌激素受体(GPER),双酚A通过依赖GPER的途径促进迁移。双酚A还诱导粘着斑激酶(FAK)、Src和细胞外信号调节激酶2(ERK2)的激活,而双酚A诱导的迁移需要这些激酶的活性。此外,双酚A通过依赖Src和ERK2的途径诱导激活蛋白-1(AP-1)和核因子κB(NFκB)与DNA的结合活性。总之,我们的研究结果表明,双酚A诱导信号转导途径的激活,这些途径介导MDA-MB-231乳腺癌细胞的迁移、AP-1/NFκB与DNA的结合活性以及侵袭过程。