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 g-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 g-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.