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

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Tumor Biology

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.

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Authors and Affiliations

  1. Department of Pathology, the First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Shenyang, 110001, China

    Yang Liu, Liang Wang, Xu-Yong Lin, Jian Wang, Juan-Han Yu, Yuan Miao & En-Hua Wang

  2. Institute of Pathology and Pathophysiology, China Medical University, Shenyang, 110001, China

    Yang Liu, Liang Wang, Xu-Yong Lin, Jian Wang, Juan-Han Yu, Yuan Miao & En-Hua Wang

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  1. Yang Liu
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  2. Liang Wang
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  4. Jian Wang
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Correspondence to En-Hua Wang.

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Liu, Y., Wang, L., Lin, XY. et al. Anti-apoptotic effect of claudin-1 on TNF-α-induced apoptosis in human breast cancer MCF-7 cells. Tumor Biol. 33, 2307–2315 (2012). https://doi.org/10.1007/s13277-012-0493-1

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  • DOI: https://doi.org/10.1007/s13277-012-0493-1

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