Document Detail


Hepatocyte growth factor activates the AP-1 complex: a comparison between normal and transformed rat hepatocytes.
MedLine Citation:
PMID:  10365821     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND/AIMS: Stimulation of activator protein-1 (AP-1), a Fos/Jun complex, is a key event in the cell response to growth factors. We have investigated whether hepatocyte growth factor (HGF) induces differential AP-1 responses in normal and transformed rat hepatocytes, the 7777 cells. METHODS: Primocultures of isolated hepatocytes or 7777 cells were stimulated with HGF. Gene expression was evaluated by ribonuclease protection assay and Western blot analysis. AP-1 DNA binding activity was measured by electrophoretic mobility shift assay. Identification of the proteins bound to the probes was made by supershift assays with specific antibodies. Cells were electroporated with plasmids containing an AP-1-dependent chloramphenicol acetyl transferase (CAT) gene, and CAT activity was measured 24 h after treatment with medium alone or HGF. RESULTS: In both cell types, HGF triggered the same program of jun family mRNA activation, but distinct Fos/Jun proteins accumulated in the nucleus. HGF increased DNA-binding activity to the phorbol 12-O-tetradecanoate-13-acetate responsive element (TRE) in both cell types, but distinct TRE-binding proteins were recruited in the AP-1 dimers. HGF also increased consistently binding to a cAMP responsive element (CRE) in hepatocytes only. Finally, HGF triggered TRE- and CRE-dependent gene activations in hepatocytes but TRE-dependent gene activation alone in 7777 cells. CONCLUSIONS: HGF-induced AP-1 activation leads to the formation of distinct dimers with different functional capacities in normal and transformed hepatocytes. These data suggest the importance of qualitative abnormalities of the AP-1 complex for the establishment or maintainance of a transformed phenotype.
Authors:
M Rahmani; F Nadori; A M Durand-Schneider; B Lardeux; D Bernuau
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of hepatology     Volume:  30     ISSN:  0168-8278     ISO Abbreviation:  J. Hepatol.     Publication Date:  1999 May 
Date Detail:
Created Date:  1999-07-23     Completed Date:  1999-07-23     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  8503886     Medline TA:  J Hepatol     Country:  DENMARK    
Other Details:
Languages:  eng     Pagination:  916-25     Citation Subset:  IM    
Affiliation:
Laboratoire de Biologie Cellulaire, INSERM U 327, Faculté de Médecine X, Bichat, Université Paris, France.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Line, Transformed
Cell Nucleus / drug effects
Cells, Cultured
Chloramphenicol O-Acetyltransferase / genetics
Dimerization
Gene Expression Regulation / drug effects*
Genes, Reporter
Genes, fos
Genes, jun
Hepatocyte Growth Factor / pharmacology*
Liver Neoplasms, Experimental
Luciferases / genetics
Male
Nuclear Proteins / metabolism
Phenotype
Proto-Oncogene Proteins c-jun / genetics
Rats
Rats, Sprague-Dawley
Tetradecanoylphorbol Acetate / pharmacology
Transcription Factor AP-1 / metabolism*
Transcription, Genetic
Transcriptional Activation
Transfection
Tumor Cells, Cultured
Chemical
Reg. No./Substance:
0/Nuclear Proteins; 0/Proto-Oncogene Proteins c-jun; 0/Transcription Factor AP-1; 16561-29-8/Tetradecanoylphorbol Acetate; 67256-21-7/Hepatocyte Growth Factor; EC 1.13.12.-/Luciferases; EC 2.3.1.28/Chloramphenicol O-Acetyltransferase

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