HER-2 promotes breast cancer cell epithelial-mesenchymal transition by regulating ZEB1 / 中国癌症杂志

ABSTRACT

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.