Regulation of MMP-9 gene expression for the development of novel molecular targets against cancer and inflammatory diseases.
The need to pharmacologically control the proteolytic activity of matrix metalloproteinases (MMPs) has been commonly acknowledged, despite its limited efficacy in clinical trials. Among the reasons that explain this failure is our limited understanding of the signals that control the expression of MMPs in different cell types during different pathological conditions. Thus, future therapies must rely on more selective approaches. With the continually increasing body of proof implicating MMPs in a large number of diseases, it has become a priority to establish the pertinence of molecules involved in the signalling pathways leading to the expression of these enzymes. MMP-9 is a case in point: its dramatic overexpression in cancer and various inflammatory conditions clearly points to the molecular mechanisms controlling its expression as a potential target for eventual rational therapeutic intervention. In this article, recent progress in the signalling pathways that regulate MMP-9 expression is reviewed, and the latest strategies to be considered in the search for a specific inhibitor of its expression are presented.
INRS-Institut Armand-Frappier, University of Quebec, 531 Boulevard des Prairies, Laval, Quebec, H7V 1B7, Canada. yves.st-pierre@inrs-iaf.uquebec.ca
Yves
Y
St-Pierre
Julie
J
Couillard
Céline
C
Van Themsche
D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001665:Binding Sites; D016384:Consensus Sequence; D015232:Dinoprostone / Q000502:physiology; D015195:Drug Design; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000145:classification / Q000494:pharmacology / Q000627:therapeutic use; D044127:Epigenesis, Genetic / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D041722:Genes, Transgenic, Suicide; D015316:Genetic Therapy; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000201:enzymology / Q000628:therapy; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000502:physiology; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000235:genetics; D061965:Matrix Metalloproteinase Inhibitors; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D008954:Models, Biological; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000502:physiology; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000628:therapy; D016376:Oligonucleotides, Antisense / Q000627:therapeutic use; D008517:Phytotherapy; D011401:Promoter Regions, Genetic; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000502:physiology
D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D061965:Matrix Metalloproteinase Inhibitors; D016328:NF-kappa B; D016376:Oligonucleotides, Antisense; D014157:Transcription Factors; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; D020780:Matrix Metalloproteinase 9; D015232:Dinoprostone