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

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.
Authors	Xiaotang Ma, Huilai Miao, Baoguo Jing, Qunwen Pan, Huiting Zhang, Yanfang Chen, Dan Zhang, Zhongzeng Liang, Zhili Wen, Mingyi Li
Journal	Oncology reports (Oncol Rep) Vol. 34 Issue 2 Pg. 681-90 (Aug 2015) ISSN: 1791-2431 [Electronic] Greece
PMID	26058359 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	CLDN4 protein, human Claudin-4
Topics	Animals Apoptosis Breast Neoplasms (genetics, metabolism, pathology) Cell Movement Cell Proliferation Claudin-4 (genetics, metabolism) DNA Methylation Female Humans MCF-7 Cells Mice Mice, Nude Neoplasm Transplantation Up-Regulation

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