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Gamma-irradiation induces matrix metalloproteinase II expression in a p53-dependent manner
1Department of Radiation Oncology, Division of Radiation and Cancer Biology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
Abstract:
Matrix metalloproteinases (MMPs) are a family of proteinases that degrade the basement membrane and have been implicated in promoting tumor metastasis. MMP-2, one member of this family, was recently found to be a p53 target and subject to p53 upregulation. In this study, we examined the correlation between the expression of MMP-2 and the increased expression of p53 after gamma-irradiation. Three human p53-positive cell lines that express wild-type p53, including U2-OS (osteosarcoma), RKO (colon carcinoma), MCF-7 (breast carcinoma), one mouse p53 positive cell line and HepG2 (liver carcinoma), and two p53-negative human cell lines, SAOS-2 (osteosarcoma) and RKO-E6 (colon carcinoma), were used in this study. The MMP-2 activity was analyzed by using gelatin zymography. The p53 level was measured by western blot analysis. Our results show that wild-type p53 induced by ionizing radiation caused a subsequent increase of MMP-2 activity in U2-OS and RKO cells but not in MCF-7, HepG2, SAOS-2, or RKO-E6 cells. These results suggest that the gamma-radiation-induced expression of MMP-2 is dependent on the cell type and presence of functional p53. Thus, ionizing radiation could activate MMP-2 activity in a subset of human cancer cells and may lead to an increase in their metastatic potential.
Insights
Gamma irradiation increases matrix metalloproteinase-2 (MMP-2) activity in some cancer cells. This effect depends on functional p53, potentially increasing tumor metastasis risk.
Area of Science:
- Oncology
- Molecular Biology
- Radiation Biology
Background:
- Matrix metalloproteinases (MMPs) degrade basement membranes, aiding tumor metastasis.
- MMP-2, a specific MMP, is a p53 target and can be upregulated by p53.
- The relationship between p53 and MMP-2 expression post-gamma irradiation requires further investigation.
Purpose of the Study:
- To investigate the correlation between MMP-2 expression and p53 levels following gamma irradiation.
- To determine if functional p53 influences MMP-2 activity after ionizing radiation exposure.
Main Methods:
- Utilized human and mouse cancer cell lines with varying p53 status (wild-type and negative).
- Analyzed MMP-2 activity using gelatin zymography.
- Quantified p53 protein levels via western blot analysis.
Main Results:
- Ionizing radiation induced increased MMP-2 activity in p53-positive U2-OS and RKO cells.
- MCF-7, HepG2, SAOS-2, and RKO-E6 cells did not show increased MMP-2 activity.
- MMP-2 induction by gamma radiation was cell-type dependent and required functional p53.
Conclusions:
- Gamma-radiation-induced MMP-2 expression is contingent on cell type and the presence of functional p53.
- Ionizing radiation can activate MMP-2 in a subset of human cancers, potentially enhancing metastatic potential.