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

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) b y specialized matrix metalloproteinases (MMPs) is another major step in tum or invasion and metastasis. We have examined, in a rat glioma cell line A15 A5, the effect of the stable transfection of human bcl-2, bar and bcl-xl on MMPs expression. Using a zymographic assay, we found that all transfected cell lines expressed a gelatinase activity which is predominantly associate d with MMP-9. In bcl-2 and bcl-xl transfected cells, the transcription of M MP-9 was decreased compared to that of control or bar transfected cells. In addition, in bar 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 b cl-2 related proteins (i.e., high ratio in bar transfected A15A5 and low ra tio in bcl-2 transfected A15A5). However, MMPs secreted by bcl-2 transfecte d cells were still capable of hydrolyzing Fast present on human lymphocytes . Our results suggest that the expression of bcl-2 related proteins could p articipate in the regulation of MMP-9/TIMP-1 in gliomas. (C) 2000 Academic Press.