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Published on: April 25, 2017
Upregulation of HES1 Promotes Cell Proliferation and Invasion in Breast Cancer as a Prognosis Marker and Therapy
Xiaoying Li1, Yu Cao1, Mu Li2
1Department of Breast Surgery, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China.
Abstract:
HES1 is a transcriptional repressor involved in cell differentiation and proliferation as well as in various cancer developments, but its expression pattern and biological roles in breast cancer have not been examined. In this study, we assessed HES1 expression in breast cancer tissues using immunohistochemistry and Western blot analyses and investigated HES1 function using MTT and Matrigel invasion assays. Significant relationships were observed between HES1 upregulation and advanced TNM stage (p=0.011), node metastasis (p=0.043), negative oestrogen receptor expression (p=0.001) and triple-negative status (p=0.001). HES1 overexpression was correlated with poor prognosis in breast cancer patients (p<0.05). The MTT and Matrigel invasion assays showed that silencing HES1 in MDA-MB-231 cells decreased cell proliferation and invasion, whereas overexpression of HES1 in MCF-7 cells enhanced its proliferation and invasion. Further analyses showed that silencing HES1 downregulated p-AKT and impeded epithelial-mesenchymal transition (EMT), whereas overexpression of HES1 upregulated AKT phosphorylation and induced EMT. Our study demonstrated that HES1 upregulation is a predictor of poor prognosis in human breast cancers and might be a critical contributor to the proliferation and invasion of breast cancer cells. Moreover, the proportion of cells with overexpression of HES1 in triple-negative breast cancer (TNBC) samples was significantly higher. Thus, HES1 might be a potential therapeutic target in the treatment of TNBC.
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