Influence of bcl-2-related proteins on matrix metalloproteinase expression in a rat glioma cell line

Biochem Biophys Res Commun. 2000 Jul 5;273(2):411-6. doi: 10.1006/bbrc.2000.2952.

Abstract

The expression of bcl-2-related proteins has been shown to be a key element in tumoral malignancy. The degradation of the extracellular matrix (ECM) by specialized matrix metalloproteinases (MMPs) is another major step in tumor invasion and metastasis. We have examined, in a rat glioma cell line A15A5, the effect of the stable transfection of human bcl-2, bax and bcl-xl on MMPs expression. Using a zymographic assay, we found that all transfected cell lines expressed a gelatinase activity which is predominantly associated with MMP-9. In bcl-2 and bcl-xl transfected cells, the transcription of MMP-9 was decreased compared to that of control or bax transfected cells. In addition, in bax transfected A15A5, we observed a down regulation of TIMP-1, the inhibitor of MMP-9. These results suggest that the ratio between MMP-9 and its inhibitor TIMP-1 is tightly controlled in cells overexpressing bcl-2 related proteins (i.e., high ratio in bax transfected A15A5 and low ratio in bcl-2 transfected A15A5). However, MMPs secreted by bcl-2 transfected cells were still capable of hydrolyzing FasL present on human lymphocytes. Our results suggest that the expression of bcl-2 related proteins could participate in the regulation of MMP-9/TIMP-1 in gliomas.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Fas Ligand Protein
  • Glioma / genetics
  • Glioma / metabolism
  • Glioma / pathology
  • Humans
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • Matrix Metalloproteinases / genetics
  • Matrix Metalloproteinases / metabolism*
  • Membrane Glycoproteins / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Tissue Inhibitor of Metalloproteinase-1 / genetics
  • Tissue Inhibitor of Metalloproteinase-1 / metabolism
  • Transfection
  • Tumor Cells, Cultured

Substances

  • FASLG protein, human
  • Fas Ligand Protein
  • Faslg protein, rat
  • Membrane Glycoproteins
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • Tissue Inhibitor of Metalloproteinase-1
  • Matrix Metalloproteinases
  • Matrix Metalloproteinase 9