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KMID : 0603820130190010001
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Journal of Experimental & Biomedical Science
2013 Volume.19 No. 1 p.1 ~ p.8
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Parkin Induces MMP-3 Expression in Human Cervical Cancer Cells
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Lee Min-Ho
Jung Byung-Chul
Jung Bae-Dong
Lee In-Soo
Rhee Ki-Jong
Kim Yoon-Suk
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Abstract
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Parkin is known to be a tumor suppressor protein. Previously, we determined that parkin expression restores susceptibility to TNF-α-induced death of HeLa cells, a human cervical cancer cell line resistant to TNF-α-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-α-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-α. 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-α-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-α-induced cell death. These results implicate a role of MMP-3 in parkin-induced cell death in TNF-α treated HeLa cells.
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KEYWORD
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Parkin, TNF-α, MMP-3, Cervical cancer, Tumor suppressor
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