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

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.

• Authors: L Oliver, K Tremblais, N Guriec, S Martin, K Meflah, J Menanteau, F M Vallette
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 273 Issue 2 Pg. 411-6 (Jul 05 2000) ISSN: 0006-291X [Print] United States
• PMID: 10873619 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2000 Academic Press.

Chemical References

• 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

Topics

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