Ornithine decarboxylase overexpression enhances ERK and p38 phosphorylation and matrix metalloproteinase-2 expression.
In the present study, we investigated the relationship between ornithine decarboxylase, MAP kinase, and MMP-2 expression in vitro. Overexpression of ornithine decarboxylase cDNA induced MMP-2 expression both at mRNA and protein levels. Promoter analysis and gel shift assay showed that p53 and Ets-1 were involved in MMP-2 expression in ornithine decarboxylase overexpressing transfectants. Erk and p38 MAP kinase were significantly activated. Using specific inhibitors of MEK and p38, we clarified that MMP-2 expression was induced via both Erk and p38 MAP kinase signaling pathways. This is the first report showing the existence of a causal relationship between ornithine decarboxylase expression, Erk and p38 MAP kinase activation, and MMP-2 expression.
Nemoto
Takahiro
T
Department of Physiological Chemistry and Metabolism, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Tokyo 113-0033, Japan.
Kubota
Shunichiro
S
D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000235:genetics* / Q000378:metabolism*; D009955:Ornithine Decarboxylase / Q000235:genetics* / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020778:Matrix Metalloproteinase 2; D009955:Ornithine Decarboxylase