title: 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.affiliation: Clinical Research Center, Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong 524001, P.R. China.
authors.forename: Xiaotang
authors.initials: X
authors.lastname: Ma
authors.affiliation: Department of Surgery, Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong 524001, P.R. China.
authors.forename: Huilai
authors.initials: H
authors.lastname: Miao
authors.affiliation: Cancer Center, Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong 524001, P.R. China.
authors.forename: Baoguo
authors.initials: B
authors.lastname: Jing
authors.affiliation: Clinical Research Center, Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong 524001, P.R. China.
authors.forename: Qunwen
authors.initials: Q
authors.lastname: Pan
authors.affiliation: Clinical Research Center, Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong 524001, P.R. China.
authors.forename: Huiting
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Clinical Research Center, Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong 524001, P.R. China.
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Cancer Center, Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong 524001, P.R. China.
authors.forename: Dan
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Surgery, Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong 524001, P.R. China.
authors.forename: Zhongzeng
authors.initials: Z
authors.lastname: Liang
authors.affiliation: Affiliated Hospital of Infectious Diseases, Nanchang University, Nanchang, Jiangxi 330002, P.R. China.
authors.forename: Zhili
authors.initials: Z
authors.lastname: Wen
authors.affiliation: Department of Surgery, Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong 524001, P.R. China.
authors.forename: Mingyi
authors.initials: M
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D002465:Cell Movement; D049109:Cell Proliferation; D062506:Claudin-4 / Q000235:genetics* / Q000378:metabolism*; D019175:DNA Methylation; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D015854:Up-Regulation
chemical_list: C568157:CLDN4 protein, human; D062506:Claudin-4