Document Detail

Type I collagen-induced pro-MMP-2 activation is differentially regulated by H-Ras and N-Ras in human breast epithelial cells.
MedLine Citation:
PMID:  17927918     Owner:  NLM     Status:  MEDLINE    
Tumor cell invasion and metastasis are often associated with matrix metalloproteinases (MMPs), among which MMP-2 and MMP-9 are of central importance. We previously showed that H-Ras, but not N-Ras, induced invasion of MCF10A human breast epithelial cells in which the enhanced expression of MMP-2 was involved. MMP-2 is produced as a latent pro-MMP-2 (72 kDa) to be activated resulting the 62 kDa active MMP-2. The present study investigated if H-Ras and/or N-Ras induces pro-MMP-2 activation of MCF10A cells when cultured in two-dimensional gel of type I collagen. Type I collagen induced activation of pro-MMP-2 only in H-Ras MCF10A cells but not in N-Ras MCF10A cells. Induction of active MMP-2 by type I collagen was suppressed by blocking integrin alpha2, indicating the involvement of integrin signaling in pro-MMP-2 activation. Membrane-type (MT)1-MMP and tissue inhibitor of metalloproteinase (TIMP)-2 were up-regulated by H-Ras but not by N-Ras in the type I collagen-coated gel, suggesting that H-Ras-specific up-regulation of MT1-MMP and TIMP-2 may lead to the activation of pro-MMP-2. Since acquisition of pro-MMP-2 activation can be associated with increased malignant progression, these results may help understanding the mechanisms for the cell surface matrix-degrading potential which will be crucial to the prognosis and therapy of breast cancer metastasis.
In Young Kim; Seo-Jin Jeong; Eun-Sook Kim; Seung Hee Kim; Aree Moon
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of biochemistry and molecular biology     Volume:  40     ISSN:  1225-8687     ISO Abbreviation:  J. Biochem. Mol. Biol.     Publication Date:  2007 Sep 
Date Detail:
Created Date:  2007-10-11     Completed Date:  2008-01-11     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9702084     Medline TA:  J Biochem Mol Biol     Country:  Korea (South)    
Other Details:
Languages:  eng     Pagination:  825-31     Citation Subset:  IM    
College of Pharmacy, Duksung Women's University, Seoul 132-714, Korea.
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MeSH Terms
Antigens, CD29 / metabolism
Cell Line
Collagen Type I / pharmacology*
Enzyme Activation / drug effects
Enzyme Precursors / metabolism*
Gelatinases / metabolism*
Integrin alpha1 / metabolism
Metalloendopeptidases / metabolism*
Time Factors
Tissue Inhibitor of Metalloproteinase-2 / metabolism
ras Proteins / metabolism,  physiology*
Reg. No./Substance:
0/Antigens, CD29; 0/Collagen Type I; 0/Enzyme Precursors; 0/Integrin alpha1; 127497-59-0/Tissue Inhibitor of Metalloproteinase-2; EC 3.4.24.-/Gelatinases; EC 3.4.24.-/Metalloendopeptidases; EC 3.4.24.-/progelatinase; EC Proteins

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