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KMID : 0617219980090010131
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Duksung Bulletin Phamaceutical Sciences
1998 Volume.9 No. 1 p.131 ~ p.137
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Roles of Matrix Metalloproteinase-2 and 9 on the H-ras-Induced Invasive Phenotype in Human Breast Epithelial Cells and Human Fibrosarcoma Cells
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Kim, Mi-Sung
Won, Ju-Hye/Moon, Aree
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Abstract
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One of the most frequent defects in human cancer is the uncontrolled activation of the rassignaling pathways. Significant evidence has accumulated to directly implicate members of the matrix metalloproteinases (MMPs) in tumor invasion and metastasis formation. We have previously shown that MMP-9 expression was significantly enhanced in the ras-tranfected HT1080 human fibrosarcoma cells at the mRNA level. In the present study, we investigated the roles of MMP-2 and -9 on the H-ras-induced invasive phenotypes of MCF10A human breast epithelial cells and HT1080 human fibrosarcoma cells. We show that H-ras is able to induce or enhance a signaling pathway leading to the enhancement of an invasive phenotype in both MCF10A and HT1080 cells as determined by matriget invasion assay. We then examined the effect of H-ras activation on the expression of MMP-2 and -9 by measuring enzymatic activities and mRNA levels. Our data clealy demonstrated that H-ras prominently induces expression of MMP-2 in MCF10A cells, while it efficiently upregulates MMP-9 in HT1080 cells. Taken together, these findings suggest that the correlation between ras-mediated invasiveness and enhanced expression of MMPs may be cell type-specific: MMP-9 is closely associated with the invasive phenotype induced by ras activation in fibrosarcoma cells, whereas MMP-2 is more likely associated with it in epithelial cells.
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