Induced expression of MMP-9 in C6 glioma cells is inhibited by PDGF via a PI 3-kinase-dependent pathway.
The involvement of phosphatidylinositol 3 (PI 3)-kinase in the signalling pathways leading to MMP-9 expression in glioma cells remains unclear. Here, we report that PI 3-kinase inhibits MMP-9 expression induced by either IL-1 or TNF-alpha in rat C6 glioma cells. Using zymography and semi-quantitative RT-PCR analysis, we showed that treatment of C6 cells with wortmannin, an inhibitor of PI 3-kinase activity, potentiated the expression of MMP-9 induced by both cytokines. In contrast, platelet-derived growth factor (PDGF), an inducer of PI 3-kinase activity in C6 cells, inhibited IL-1- or TNF-alpha-induced MMP-9 secretion. Accordingly, this inhibition by PDGF was prevented by wortmannin. Furthermore, stable C6 clones over-expressing the dominant-negative form the regulatory subunit of PI 3-kinase potentiated the expression of MMP-9 induced by IL-1 or TNF-alpha. Taken together, these results suggest that PI 3-kinase may act as a negative regulator of MMP-9 expression in C6 glioma cells.
INRS-Institut Armand-Frappier, Université du Québec, 531 Boulevard des-Prairies, Laval, Québec, Canada H7V 1B7.
Pierre-Olivier
PO
Estève
Olivier
O
Robledo
Edouard F
EF
Potworowski
Yves
Y
St-Pierre
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D005799:Genes, Dominant; D007375:Interleukin-1 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012313:RNA / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000077191:Wortmannin
D000730:Androstadienes; D016207:Cytokines; D004791:Enzyme Inhibitors; D007375:Interleukin-1; D010982:Platelet-Derived Growth Factor; D014409:Tumor Necrosis Factor-alpha; D012313:RNA; D019869:Phosphatidylinositol 3-Kinases; D020780:Matrix Metalloproteinase 9; D000077191:Wortmannin