Cell-specific regulation of proliferation by Ano1/TMEM16A in breast cancer with different ER, PR, and HER2 status.
Cell-specific regulation of proliferation by Ano1/TMEM16A in breast cancer with different ER, PR, and HER2 status.
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Ano1/TMEM16A 对不同 ER、PR 和 HER2 状态乳腺癌中增殖的细胞特异性调节
DOI：
10.18632/oncotarget.18662
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发表时间：
2017-10-17
期刊：
影响因子：
--
通讯作者：
Wei M
中科院分区：
文献类型：
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作者：
Wu H;Wang H;Guan S;Zhang J;Chen Q;Wang X;Ma K;Zhao P;Zhao H;Yao W;Jin F;Xiao Q;Wei M
钙激活氯离子通道Ano 1（TMEM 16 A）在许多肿瘤中过表达。然而，关于Ano 1在细胞增殖中的作用存在相互矛盾的数据。在这里，我们进行免疫组织化学研究Ano 1和Ki 67在403例乳腺癌患者中的表达，并分析Ano 1和Ki 67在乳腺癌亚型中的表达之间的相关性，这些乳腺癌亚型根据雌激素受体（ER）、孕激素受体（PR）和人表皮生长因子受体2（HER 2）进行分类。Ano 1表达与Ki 67表达呈负相关。ER阳性或HER 2阴性的Ki 67低表达患者中Ano 1过表达更频繁。在Ki 67低表达的乳腺癌中，Ano 1过表达与较长的总生存期（OS）相关，尤其是在ER阳性、PR阳性和HER 2阴性乳腺癌中。多变量考克斯回归分析显示，Ano 1过表达是Ki 67低表达的ER阳性、PR阳性或HER 2阴性患者总生存期延长的预后因素。此外，Ano 1促进ER阳性、PR阳性和HER 2阴性MCF 7细胞的细胞增殖，但抑制ER阴性、PR阴性和HER 2阴性MDA-MB-435 S细胞的细胞增殖。我们的研究结果表明，Ano 1可能差异调节乳腺癌的ER，PR和HER 2亚型的细胞增殖。Ano 1和Ki 67的联合表达可用于预测具有不同ER、PR和HER 2亚型的乳腺癌患者的临床结局。
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.