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Article

CLDN6-induced apoptosis via regulating ASK1-p38/JNK signaling in breast cancer MCF-7 cells

  • Authors:
    • Yaxiong Guo
    • Dongjing Lin
    • Mingzi Zhang
    • Xiaowei Zhang
    • Yanru Li
    • Ruan Yang
    • Yan Lu
    • Xiangshu Jin
    • Minlan Yang
    • Miaomiao Wang
    • Shuai Zhao
    • Chengshi Quan
  • View Affiliations / Copyright

    Affiliations: The Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medical Sciences, Jilin University, Changchun, Jilin 130021, P.R. China
  • Pages: 2435-2444
    |
    Published online on: April 1, 2016
       https://doi.org/10.3892/ijo.2016.3469
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Abstract

Claudin 6 (CLDN6), a member of tight junction protein claudin (CLDN) family, inhibits proliferation and induces apoptosis of MCF-7 breast cancer cells. However, these molecular mechanisms of CLDN6-induced apoptosis remain largely elusive. We previously found that restoration of human CLDN6 gene expression was correlated with the expression level of apoptosis signal-regulating kinase 1 (ASK1) using cDNA array and bioinformatics analysis. ASK1, a mitogen-activated protein kinase kinase kinase, is involved in environmental stress-activation of the c-jun N-terminal kinase (JNK) and p38 pathways, which contribute to apoptosis-associated tumor cell death. In the present study, we show that the restoration of CLDN6 gene expression in MCF-7 cells marhedly decreased ASK1 phosphorylation at Ser967. Activated ASK1ser967 further induced the activation of downstream targets, JNK and p38 kinase. MCF-7/CLDN6 stable transfection cell clone treated with TRX1, an ASK1 inhibitor, showed suppressed JNK and p38 activation, and showed substantially increased survival and colony formation and reduced percent of apoptotic cells using TUNEL staining and DNA ladder. Furthermore, TRX1 treatment increased Bcl-2/Bax ratio and reduced caspase-3 cleavage in MCF-7/CLDN6 stable transfection cell clone. Therefore, these data show that CLDN6 mediates ASK1-p38/JNK apoptotic signaling in MCF-7 cells, and it is correlated with constitutive deregulation of the balance of Bcl-2 family proteins and activation of caspase-3.
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Copy and paste a formatted citation
Spandidos Publications style
Guo Y, Lin D, Zhang M, Zhang X, Li Y, Yang R, Lu Y, Jin X, Yang M, Wang M, Wang M, et al: CLDN6-induced apoptosis via regulating ASK1-p38/JNK signaling in breast cancer MCF-7 cells. Int J Oncol 48: 2435-2444, 2016.
APA
Guo, Y., Lin, D., Zhang, M., Zhang, X., Li, Y., Yang, R. ... Quan, C. (2016). CLDN6-induced apoptosis via regulating ASK1-p38/JNK signaling in breast cancer MCF-7 cells. International Journal of Oncology, 48, 2435-2444. https://doi.org/10.3892/ijo.2016.3469
MLA
Guo, Y., Lin, D., Zhang, M., Zhang, X., Li, Y., Yang, R., Lu, Y., Jin, X., Yang, M., Wang, M., Zhao, S., Quan, C."CLDN6-induced apoptosis via regulating ASK1-p38/JNK signaling in breast cancer MCF-7 cells". International Journal of Oncology 48.6 (2016): 2435-2444.
Chicago
Guo, Y., Lin, D., Zhang, M., Zhang, X., Li, Y., Yang, R., Lu, Y., Jin, X., Yang, M., Wang, M., Zhao, S., Quan, C."CLDN6-induced apoptosis via regulating ASK1-p38/JNK signaling in breast cancer MCF-7 cells". International Journal of Oncology 48, no. 6 (2016): 2435-2444. https://doi.org/10.3892/ijo.2016.3469
Copy and paste a formatted citation
x
Spandidos Publications style
Guo Y, Lin D, Zhang M, Zhang X, Li Y, Yang R, Lu Y, Jin X, Yang M, Wang M, Wang M, et al: CLDN6-induced apoptosis via regulating ASK1-p38/JNK signaling in breast cancer MCF-7 cells. Int J Oncol 48: 2435-2444, 2016.
APA
Guo, Y., Lin, D., Zhang, M., Zhang, X., Li, Y., Yang, R. ... Quan, C. (2016). CLDN6-induced apoptosis via regulating ASK1-p38/JNK signaling in breast cancer MCF-7 cells. International Journal of Oncology, 48, 2435-2444. https://doi.org/10.3892/ijo.2016.3469
MLA
Guo, Y., Lin, D., Zhang, M., Zhang, X., Li, Y., Yang, R., Lu, Y., Jin, X., Yang, M., Wang, M., Zhao, S., Quan, C."CLDN6-induced apoptosis via regulating ASK1-p38/JNK signaling in breast cancer MCF-7 cells". International Journal of Oncology 48.6 (2016): 2435-2444.
Chicago
Guo, Y., Lin, D., Zhang, M., Zhang, X., Li, Y., Yang, R., Lu, Y., Jin, X., Yang, M., Wang, M., Zhao, S., Quan, C."CLDN6-induced apoptosis via regulating ASK1-p38/JNK signaling in breast cancer MCF-7 cells". International Journal of Oncology 48, no. 6 (2016): 2435-2444. https://doi.org/10.3892/ijo.2016.3469
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