Linked Life Data

10996658

Source:http://linkedlifedata.com/resource/pubmed/id/10996658

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2000-11-28
pubmed:abstractText
Matrix metalloproteinase-2 (MMP-2) has been suggested to play a crucial role in tumor invasion and angiogenesis. In order to understand the mechanisms underlying proMMP-2 activation, we compared the biochemical and cellular events triggered by two potent MMP-2 activators, the lectin concanavalin A (ConA) and the cytoskeleton disrupting agent cytochalasin D (CytoD). Incubation of U87 human glioma cells for 24 h in the presence of ConA or CytoD induced a marked activation of proMMP-2 and this activation was correlated in both cases with an increase in the mRNA levels of MT1-MMP. At the protein level, proMMP-2 activation induced by CytoD or ConA strongly correlated with the appearance of a 43-kDa MT1-MMP proteolytic breakdown product in cell lysates. Interestingly, CytoD also induced a very rapid (2 h) activation of proMMP-2 that was independent of protein synthesis. Under these conditions, CytoD also promoted the rapid proteolytic breakdown of the 63 kDa pro form of MT1-MMP, resulting in the appearance of the 43 kDa MT1-MMP processed form. Overexpression of a recombinant full-length MT1-MMP protein in glioma cells resulted in the activation of proMMP-2 that was correlated with the generation of the 43 kDa fragment of the protein. By contrast, overexpression of the protein in COS-7 cells promoted proMMP-2 activation without inducing the production of the 43 kDa fragment. These results thus suggest that activation of proMMP-2 occurs through both translational and post-translational mechanisms, both involving proteolytic processing of membrane-associated MT1-MMP. This processing of MT1-MMP is, however, not essential to proMMP-2 activation but may represent a regulatory mechanism to control the activity of MT1-MMP.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0006-3002
pubmed:author
pubmed:issnType
Print
pubmed:day
20
pubmed:volume
1497
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
341-50
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:10996658-Concanavalin A, pubmed-meshheading:10996658-Culture Media, Conditioned, pubmed-meshheading:10996658-Cytochalasin D, pubmed-meshheading:10996658-Enzyme Activation, pubmed-meshheading:10996658-Enzyme Inhibitors, pubmed-meshheading:10996658-Extracellular Matrix Proteins, pubmed-meshheading:10996658-Gene Expression Regulation, Enzymologic, pubmed-meshheading:10996658-Glioma, pubmed-meshheading:10996658-Humans, pubmed-meshheading:10996658-Immunoblotting, pubmed-meshheading:10996658-Matrix Metalloproteinase 2, pubmed-meshheading:10996658-Matrix Metalloproteinases, Membrane-Associated, pubmed-meshheading:10996658-Metalloendopeptidases, pubmed-meshheading:10996658-Protein Precursors, pubmed-meshheading:10996658-RNA, Messenger, pubmed-meshheading:10996658-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:10996658-Signal Transduction, pubmed-meshheading:10996658-Tumor Cells, Cultured
pubmed:year
2000
pubmed:articleTitle
Rapid activation of matrix metalloproteinase-2 by glioma cells occurs through a posttranslational MT1-MMP-dependent mechanism.
pubmed:affiliation
Laboratoire de Médecine Moléculaire Ste-Justine-UQAM, Centre de Cancérologie Charles-Bruneau, Hôpital Ste-Justine et Université du Québec à Montréal, C.P. 8888, Succ. Centre-ville, Québec H3C 3P8, Montréal, Canada.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't