title: Anti-apoptotic effect of claudin-1 on TNF-α-induced apoptosis in human breast cancer MCF-7 cells.
abstract: Accumulating evidence reveals that aberrant expression of claudins manifests in various tumors; however, their biological functions are poorly understood. Here, we report on the elevated expression of claudin-1 in human breast cancer MCF-7 cells under tumor necrosis factor (TNF)-α treatment. Interestingly, the increased expression of claudin-1 contributes to an anti-apoptotic role in TNF-α-induced apoptosis. In line with this, upon TNF-α stimulus, downregulation of claudin-1 by siRNA knockdown results in a significant increase in cleavage of caspase-8 and poly (ADP-ribose) polymerase, a decrease of cyclinD1 expression, and DNA fragmentation. Consistently, TdT-mediated dUTP nick end labeling assay also shows that loss of claudin-1 increases the susceptibility of MCF-7 cells to TNF-α-induced apoptosis. However, there is no obvious effect on the expression of Bax and p53 after the treatment aforementioned. In addition, TNF-α increases the amount of claudin-1 and the cytoplasmic accumulation of β-catenin, while claudin-1 siRNA increases the amount of β-catenin in the cell membrane as well as the amount of E-cadherin in the cytoplasm. In conclusion, our data reveal a novel role of claudin-1 in regulating apoptosis in MCF-7 cells.
authors.affiliation: Department of Pathology, the First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Shenyang 110001, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.forename: Xu-Yong
authors.initials: XY
authors.lastname: Lin
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Juan-Han
authors.initials: JH
authors.lastname: Yu
authors.forename: Yuan
authors.initials: Y
authors.lastname: Miao
authors.forename: En-Hua
authors.initials: EH
authors.lastname: Wang
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D002462:Cell Membrane; D049109:Cell Proliferation / Q000187:drug effects; D062445:Claudin-1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D003593:Cytoplasm; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D021381:Protein Transport; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013347:Subcellular Fractions; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D015820:Cadherins; D062445:Claudin-1; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha; D051176:beta Catenin; D020169:Caspases