Parkin Induces MMP-3 Expression in Human Cervical Cancer Cells

  • Lee, Min Ho (Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University) ;
  • Jung, Byung Chul (Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University) ;
  • Jung, Bae Dong (College of Veterinary Medicine, Kangwon National University) ;
  • Lee, In-Soo (Department of Clinical Laboratory Science, Hyejeon College) ;
  • Rhee, Ki-Jong (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 : 2013.03.10
  • Accepted : 2013.03.17
  • Published : 2013.03.31

Abstract

Parkin is known to be a tumor suppressor protein. Previously, we determined that parkin expression restores susceptibility to TNF-${\alpha}$-induced death of HeLa cells, a human cervical cancer cell line resistant to TNF-${\alpha}$-induced cell death. MMP-3 is a zinc-dependent protease recently reported to activate intracellular apoptotic signaling. In this study we examined the regulation of MMP-3 expression by parkin in TNF-${\alpha}$-treated HeLa cells. Furthermore, we investigated the signaling pathway involved in parkin-induced expression of MMP-3. We found that HeLa cells exhibit low levels of MMP-3 but is induced after introduction of the parkin gene into HeLa cells. Furthermore, MMP-3 expression increased further when parkin expressing cells were treated with TNF-${\alpha}$. Using chemical inhibitors of cell signaling pathways, we found that MEK-1 (PD98059), PI3K (LY294002), p38 MAPK (SB203580), and JNK inhibitors alleviated parkin-induced up-regulation of MMP-3. Finally, we show that TNF-${\alpha}$-induced cell death in parkin expressing cells is inhibited by using a MMP-3 inhibitor. These results suggest that parkin expression induces prolonged expression of MMP-3 via MEK-1, PI3K, MAPK, and JNK pathway in HeLa cells allowing the HeLa cells to become sensitive to TNF-${\alpha}$-induced cell death. These results implicate a role of MMP-3 in parkin-induced cell death in TNF-${\alpha}$ treated HeLa cells.

Keywords

Acknowledgement

Supported by : National Research Foundation of Korea (NRF)

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