Anti-apoptotic effect of claudin-1 on TNF-α-induced apoptosis in human breast cancer MCF-7 cells

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作者：

Y Liu，L Wang，XY Lin，J Wang，JH Yu，Y Miao，EH Wang

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摘要：

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.

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关键词：

Claudin-1 Tumor necrosis factor-α MCF-7 Poly (ADP-ribose) polymerase

DOI：

10.1007/s13277-012-0493-1

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年份：

2012