Gamma-irradiation induces matrix metalloproteinase II expression in a p53-dependent manner

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J L Wang1, Y Sun, S Wu

  • 1Department of Radiation Oncology, Division of Radiation and Cancer Biology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.

Molecular Carcinogenesis
|April 4, 2000
PubMed

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.

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