HER-2通过ZEB1促进乳腺癌细胞上皮间质转化

背景与目的：人类表皮生长因子受体2(human epidermal growth factor receptor-2，HER-2)是表皮生长因子受体家族中的一员，它参与细胞多个生物过程，如细胞增殖、侵袭和凋亡等。有研究表明，HER-2与细胞上皮间质转化(epithelial-mesenchymal transition，EMT)过程相关，但具体机制有待进一步探讨，本研究旨在探讨HER-2对EMT的调节机制。方法：用Transwell小室模拟细胞的迁徙侵袭能力；采用实时荧光定量聚合酶链反应(real-time lfuorescent quantitative polymerase chain reaction，RTFQ-PCR)检测目的基因的表达；用活性氧检测试剂盒检测细胞活性氧的水平。结果：Transwell小室模拟实验发现，HER-2过表达能促进乳腺癌细胞的侵袭转移；机制研究表明，HER-2能上调ZEB1，用siRNA降低ZEB1表达使HER-2过表达细胞的侵袭能力受损；此外，HER-2过表达乳腺癌细胞中活性氧水平较低。结论：HER-2可以上调ZEB1的表达而赋予乳腺癌细胞EMT相关特性，ZEB1可作为进一步研究HER-2与EMT调节关系的靶点。

HER-2 promotes breast cancer cell epithelial-mesenchymal transition by regulating ZEB1

Background and purpose:Human epidermal growth factor receptor-2 (HER-2), a member of epidermal growth factor receptor family, initiates a diverse set of signaling pathways that ultimately affect such fun-damental processes as cell proliferation, cell motility and cell apoptosis. It is reported that HER-2 was associated with epithelial-mesenchymal transition (EMT) process. However, the mechanism needs further investigation. The purpose of this study was to investigate the mechanism of HER-2 on regulating EMT process.Methods:Transwell assay was used to determine the motility of breast cancer cells; Real-time lfuorescence quantitative polymerase chain reaction (RT-FQ-PCR) was employed to determine the expression of genes of interest, and reactive oxygen species production was measured by reactive oxygen species detection kit.Results:HER-2 overexpression in breast cancer cells could promote cell migration and invasion. Mechanistic study showed that HER-2 overexpression could upregulate ZEB1 expression. ZEB1 silencing by siRNA reduced cell motility of HER-2-overexpressing breast cancer cells. Furthermore, reactive oxygen species produced in HER-2-overexpressing breast cancer cells were less than those produced in corresponding control cells.Conclusion:Our study demonstrated that HER-2 overexpression endowed breast cancer cells with EMT related properties by upregulating ZEB1 expression. ZEB1 could be a candidate target for further study of the relation-ship between HER-2 and EMT.