Document Detail

Bcl-w promotes gastric cancer cell invasion by inducing matrix metalloproteinase-2 expression via phosphoinositide 3-kinase, Akt, and Sp1.
MedLine Citation:
PMID:  16707418     Owner:  NLM     Status:  MEDLINE    
Given a previous report that Bcl-w is expressed in gastric cancer cells, particularly in those of an infiltrative morphology, we investigated whether Bcl-w expression influences the invasiveness of gastric cancer cells. To accomplish this, Bcl-w was overexpressed in adherent types of gastric adenocarcinoma cell lines, and this was found to result in an increase in their migratory and invasive potentials. These effects were not induced when Bcl-2 was overexpressed in the same cell types. Consistently, Bcl-w, but not Bcl-2, overexpression increased matrix metalloproteinase-2 (MMP-2) expression, and synthetic or natural inhibitors of MMP-2 abolished Bcl-w-induced cell invasion. Bcl-w overexpression also activated phosphoinositide 3-kinase (PI3K), Akt, and Sp1, and the blocking effects of each of these components using pharmacologic inhibitors, dominant-negative mutants, or small interfering RNA abolished the ability of Bcl-w to induce MMP-2 and cell invasion. The inhibition of PI3K/Akt signaling also prevented Sp1 activation. Overall, our data suggest that Bcl-w, which was previously shown to enhance gastric cancer cell survivability, also promotes their invasiveness by inducing MMP-2 expression via the sequential actions of PI3K, Akt, and Sp1.
In Hwa Bae; Myung-Jin Park; Sung Hwan Yoon; Sung Wook Kang; Seung-Sook Lee; Kyung-Mi Choi; Hong-Duck Um
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cancer research     Volume:  66     ISSN:  0008-5472     ISO Abbreviation:  Cancer Res.     Publication Date:  2006 May 
Date Detail:
Created Date:  2006-05-18     Completed Date:  2006-07-18     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4991-5     Citation Subset:  IM    
Laboratory of Radiation Tumor Physiology, Functional Genomics, and Experimental Pathology, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.
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MeSH Terms
1-Phosphatidylinositol 3-Kinase / metabolism*
Adenocarcinoma / enzymology,  pathology
Apoptosis Regulatory Proteins / biosynthesis,  genetics,  metabolism*
Cell Line, Tumor
Enzyme Induction
Matrix Metalloproteinase 2 / biosynthesis*
Neoplasm Invasiveness
Proto-Oncogene Proteins c-akt / metabolism*
Proto-Oncogene Proteins c-bcl-2 / metabolism
Sp1 Transcription Factor / metabolism*
Stomach Neoplasms / enzymology,  genetics,  metabolism*,  pathology*
Reg. No./Substance:
0/Apoptosis Regulatory Proteins; 0/BCL2L2 protein, human; 0/Proto-Oncogene Proteins c-bcl-2; 0/Sp1 Transcription Factor; EC 3-Kinase; EC Proteins c-akt; EC Metalloproteinase 2

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