期刊
ONCOTARGET
卷 8, 期 49, 页码 84996-85013出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.18662
关键词
Ano1; TMEM16A; Ki67; breast cancer; proliferation
资金
- National Natural Science Foundation of the People's Republic of China [31371145, 81572613, 81402948]
- Liaoning Key Laboratory of Molecular Targeted Anti-tumor Drug Development and Evaluation Program
- Educational Commission of Liaoning Province, China [L2014315]
- Research Fund for the Doctoral Program of Higher Education of Liaoning Province, China [20141032]
- Key Laboratory Foundation from Shenyang ST Projects [F16-094-1-00]
- Liaoning Province Scientific Research Foundation [2014226033]
- Program for Liaoning Innovative Research Team in University [LT2014016]
- S&T Projects in Shenyang, China [F14-232-6-05]
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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