Claudin-4 controls the proliferation, apoptosis, migration and in vivo growth of MCF-7 breast cancer cells

Ma,Xiaotang; Miao,Huilai; Jing,Baoguo; Pan,Qunwen; Zhang,Huiting; Chen,Yanfang; Zhang,Dan; Liang,Zhongzeng; Wen,Zhili; Li,Mingyi

doi:10.3892/or.2015.4037

Claudin-4 controls the proliferation, apoptosis, migration and in vivo growth of MCF-7 breast cancer cells

Authors:
- Xiaotang Ma
- Huilai Miao
- Baoguo Jing
- Qunwen Pan
- Huiting Zhang
- Yanfang Chen
- Dan Zhang
- Zhongzeng Liang
- Zhili Wen
- Mingyi Li
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Affiliations: Clinical Research Center, Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong 524001, P.R. China, Department of Surgery, Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong 524001, P.R. China, Cancer Center, Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong 524001, P.R. China, Affiliated Hospital of Infectious Diseases, Nanchang University, Nanchang, Jiangxi 330002, P.R. China
Published online on: June 5, 2015 https://doi.org/10.3892/or.2015.4037
Pages: 681-690

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Abstract

Previous studies have shown that the expression of claudin-4 is upregulated in breast cancer. The aim of the present study was to investigate the role and the regulation of claudin-4 in MCF-7 breast cancer cells. For the in vitro experiments, MCF-7 cells were treated with recombinant vectors carrying cDNA for claudin-4 overexpression or short hairpin RNAs (shRNAs) for claudin-4 silencing. Cell proliferation was determined by an MTT assay and cell migration ability was measured by a wound-healing assay. The cell cycle profile and apoptotic rate were analyzed using flow cytometry. The effect of methylation status on claudin-4 expression was determined by PCR and western blotting. For the in vivo tumorigenesis analysis, MCF-7 cells with or without claudin-4 silencing were transplanted into nude mice. In vivo cell growth was evaluated 14 days after transplantation. We found that claudin-4 overexpression increased MCF-7 cell proliferation and migration, and reduced the rate of cell apoptosis. Silencing of claudin-4 induced the opposite effects in MCF-7 cells. In addition, claudin-4 expression was upregulated by demethylation. Moreover, the size of tumor formation was reduced in nude mice transplanted with claudin-4 silenced MCF-7 cells. These observations suggested that claudin-4, which was regulated by methylation status, plays an important role in breast cancer growth and malignancy via the control of cell proliferation, migration and apoptosis.

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