Cell-specific regulation of proliferation by Ano1/TMEM16A in breast cancer with different ER, PR, and HER2 status
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Huizhe Wu1, Hui Wang2, Shu Guan3, Jing Zhang1, Qiuchen Chen1, Xiaodong Wang1, Ke Ma2, Pengfei Zhao1, Haishan Zhao1, Weifan Yao1, Feng Jin3, Qinghuan Xiao2 and Minjie Wei1
1Department of Pharmacology, Liaoning Key Laboratory of Molecular Targeted Anti-Tumor Drug Development and Evaluation, China Medical University, Shenyang, 110122, P.R. China
2Department of Ion Channel Pharmacology, School of Pharmacy, China Medical University, Shenyang, 110122, P.R. China
3Department of Breast Surgery, The First Hospital of China Medical University, Shenyang, 110001, P.R. China
Minjie Wei, email: [email protected]
Qinghuan Xiao, email: [email protected]
Keywords: Ano1, TMEM16A, Ki67, breast cancer, proliferation
Received: October 07, 2015 Accepted: May 23, 2017 Published: June 27, 2017
The calcium-activated chloride channel Ano1 (TMEM16A) is overexpressed in many tumors. However, conflicting data exist regarding the role of Ano1 in cell proliferation. Here, we performed immunohistochemistry to investigate the expression of Ano1 and Ki67 in 403 patients with breast cancer, and analyzed the association between the expression of Ano1 and Ki67 in breast cancer subtypes categorized according to estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Ano1 expression was negatively correlated with Ki67 expression. Ano1 overexpression more frequently occurred in ER-positive or HER2-negative patients with the low expression of Ki67. Ano1 overexpression was associated with longer overall survival (OS) in breast cancer with the low expression of Ki67, especially in ER-positive, PR-positive, and HER2-negative breast cancer. Multivariate Cox regression analysis showed that Ano1 overexpression was a prognostic factor for longer overall survival in ER-positive, PR-positive, or HER2-negative patients with the low expression of Ki67. Furthermore, Ano1 promoted cell proliferation in ER-positive, PR-positive, and HER2-negative MCF7 cells, but inhibited cell proliferation in ER-negative, PR-negative, and HER2-negative MDA-MB-435S cells. Our findings suggest that Ano1 may differentially regulate cell proliferation in a subtype of breast cancer defined by ER, PR, and HER2. Combined expression of Ano1 and Ki67 may be used for predicting clinical outcomes of breast cancer patients with different subtypes of ER, PR, and HER2.
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