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Parkin induces apoptotic cell death in TNF-α-treated cervical cancer cells

  • Lee, Kyung-Hong (Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University) ;
  • Lee, Min-Ho (Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University) ;
  • Kang, Yeo-Wool (Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University) ;
  • Rhee, Ki-Jong (Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University) ;
  • Kim, Tae-Ue (Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University) ;
  • Kim, Yoon-Suk (Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University)
  • Received : 2012.05.11
  • Accepted : 2012.06.04
  • Published : 2012.09.30

Abstract

Many malignant tumors become resistant to tumor necrosis factor-alpha (TNF-${\alpha}$)-induced cell death during carcinogenesis. In the present study, we examined whether parkin acts as a tumor suppressor in HeLa cells, a human cervical cancer cell line resistant to TNF-${\alpha}$-induced cell death. TNF-${\alpha}$-treatment alone did not affect HeLa cell viability. However, expression of parkin restored TNF-${\alpha}$-induced apoptosis in HeLa cells. Increased cell death was due to the activation of the apoptotic pathway. Expression of parkin in TNF-${\alpha}$-treated HeLa cells stimulated cleavage of the pro-apoptotic proteins caspase-8, -9, -3, -7 and poly ADP ribose polymerase (PARP). In addition, parkin expression resulted in decreased expression of the caspase inhibitory protein, survivin. These results suggest that parkin acts as a tumor suppressor in human cervical cancer cells by modulating survivin expression and caspase activity. We propose that this pathway is a novel molecular mechanism by which parkin functions as a tumor suppressor.

Keywords

References

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