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Gamma‐irradiation induces matrix metalloproteinase II expression in a p53‐dependent manner
Author(s) -
Wang JuLin,
Sun Yi,
Wu Shiyong
Publication year - 2000
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/(sici)1098-2744(200004)27:4<252::aid-mc2>3.0.co;2-3
Subject(s) - biology , matrix metalloproteinase , cancer research , zymography , cell culture , downregulation and upregulation , metastasis , western blot , cancer , gene , genetics
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 γ‐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 γ‐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. Mol. Carcinog. 27:252–258, 2000. © 2000 Wiley‐Liss, Inc.