Document Detail

Hypoxia-induced bFGF gene expression is mediated through the JNK signal transduction pathway.
MedLine Citation:
PMID:  10705989     Owner:  NLM     Status:  MEDLINE    
Although the synthesis of angiogenic factors in hypoxic regions of solid tumors is recognized as one of the critical steps in tumor growth and metastasis, the signal transduction pathway involved in hypoxic induction of basic fibroblast growth factor (bFGF) gene expression is still obscure. In the study described here, we investigated the intracellular responses to hypoxia and the mechanisms triggering the initiation of angiogenic activity in drug-resistant human breast carcinoma MCF-7/ADR cells. Northern blots showed an increase in the level of c-jun, c-fos, and bFGF mRNA during hypoxia. Gel mobility-shift analysis of nuclear extracts from hypoxia-exposed cells showed an increase in AP-1 binding activity. In addition, hypoxic treatment strongly activated c-Jun N-terminal kinase 1 (JNK1), leading to phosphorylation and activation of c-Jun. Expression of a dominant negative mutant of JNK1 suppressed hypoxia-induced JNK1 activation as well as bFGF gene expression. Taken together, hypoxia-induced bFGF gene expression is mediated through the stress-activated protein kinase (SAPK) signal transduction pathway.
Y J Le; P M Corry
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Molecular and cellular biochemistry     Volume:  202     ISSN:  0300-8177     ISO Abbreviation:  Mol. Cell. Biochem.     Publication Date:  1999 Dec 
Date Detail:
Created Date:  2000-04-11     Completed Date:  2000-04-11     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0364456     Medline TA:  Mol Cell Biochem     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  1-8     Citation Subset:  IM    
Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan 48073, USA.
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MeSH Terms
Breast Neoplasms
Cell Hypoxia*
Drug Resistance, Multiple
Fibroblast Growth Factor 2 / biosynthesis,  genetics*
Gene Expression Regulation, Neoplastic*
Genes, fos
Genes, jun
JNK Mitogen-Activated Protein Kinases
Mitogen-Activated Protein Kinases / metabolism*
Neovascularization, Pathologic
Proto-Oncogene Proteins c-fos / genetics
Proto-Oncogene Proteins c-jun / genetics
RNA, Messenger / genetics
Recombinant Proteins / biosynthesis
Signal Transduction*
Transcription Factor AP-1 / metabolism
Transcription, Genetic
Tumor Cells, Cultured
Grant Support
Reg. No./Substance:
0/Proto-Oncogene Proteins c-fos; 0/Proto-Oncogene Proteins c-jun; 0/RNA, Messenger; 0/Recombinant Proteins; 0/Transcription Factor AP-1; 103107-01-3/Fibroblast Growth Factor 2; EC Mitogen-Activated Protein Kinases; EC Protein Kinases

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