Inhibition of the p38 mitogen-activated protein kinase by SB 203580 blocks PMA-induced Mr 92,000 type IV collagenase secretion and in vitro invasion.

Détails

ID Serval
serval:BIB_B519D08E9E82
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Inhibition of the p38 mitogen-activated protein kinase by SB 203580 blocks PMA-induced Mr 92,000 type IV collagenase secretion and in vitro invasion.
Périodique
Cancer Research
Auteur(s)
Simon C., Goepfert H., Boyd D.
ISSN
0008-5472 (Print)
ISSN-L
0008-5472
Statut éditorial
Publié
Date de publication
1998
Volume
58
Numéro
6
Pages
1135-1139
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.Publication Status: ppublish
Résumé
Although the p38 mitogen-activated protein kinase (MAPK) has been implicated in signal transduction events, its role in regulating the Mr 92,000 type IV collagenase matrix metalloprotease-9 (MMP-9) and in vitro invasiveness in cancer has not yet been determined. We made the surprising observation that, in a human squamous cell carcinoma cell line (UM-SCC-1), phorbol ester-enhanced MMP-9 secretion and in vitro invasiveness were associated with a strong activation of the p38 MAPK and its downstream target, MAPK-activated protein kinase-2. To determine the role of p38 activation in these events, we investigated the effect of SB 203580, a novel specific p38 inhibitor, on protease expression and in vitro invasion of these cells. We found that inhibition of p38 by SB 203580 resulted in the almost complete reduction of phorbol myristate acetate-induced MMP-9 secretion but not of urokinase-type plasminogen activator secretion. In contrast, the activation of a transiently transfected wild-type MMP-9 promoter by MEKK-1, a specific c-Jun NH2-terminal kinase activator, was only marginally inhibited by the compound, arguing for the specificity of SB 203580. Moreover, phorbol myristate acetate-enhanced in vitro invasion was completely blocked by SB 203580, whereas p38 inhibition had little effect on growth. These findings suggest that activation of p38 may contribute to a more invasive phenotype in vitro, possibly via the expression of MMP-9, and that targeting of p38 using SB 203580 may provide a novel means of controlling invasion of cancers in which this MAPK is activated.
Mots-clé
Calcium-Calmodulin-Dependent Protein Kinases/metabolism, Carcinoma, Squamous Cell/enzymology, Carcinoma, Squamous Cell/pathology, Collagenases/secretion, Enzyme Activation, Enzyme Inhibitors/pharmacology, Flavonoids/pharmacology, Head and Neck Neoplasms/pathology, Humans, Imidazoles/pharmacology, JNK Mitogen-Activated Protein Kinases, MAP Kinase Kinase 1, Matrix Metalloproteinase 9, Mitogen-Activated Protein Kinase 3, Mitogen-Activated Protein Kinase 9, Mitogen-Activated Protein Kinase Kinases, Mitogen-Activated Protein Kinases, Neoplasm Invasiveness, Protein Kinases/metabolism, Protein-Serine-Threonine Kinases/metabolism, Protein-Tyrosine Kinases/metabolism, Pyridines/pharmacology, Signal Transduction, Tetradecanoylphorbol Acetate/pharmacology, Tumor Cells, Cultured/cytology, Tumor Necrosis Factor-alpha/pharmacology, p38 Mitogen-Activated Protein Kinases
Pubmed
Web of science
Création de la notice
21/01/2013 13:51
Dernière modification de la notice
20/08/2019 15:23
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