Linked Life Data

12447692

Source:http://linkedlifedata.com/resource/pubmed/id/12447692

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2002-11-26
pubmed:abstractText
Inappropriate activation of the Wnt/beta-catenin signaling has been implicated in the development of hepatocellular carcinoma (HCC), but exactly how beta-catenin works remains to be elucidated. To identify, in vivo, the target genes of beta-catenin in the liver, we have used the suppression subtractive hybridization technique and transgenic mice expressing an activated beta-catenin in the liver that developed hepatomegaly. We identified three genes involved in glutamine metabolism, encoding glutamine synthetase (GS), ornithine aminotransferase (OAT) and the glutamate transporter GLT-1. By Northern blot and immunohistochemical analysis we demonstrated that these three genes were specifically induced by activation of the beta-catenin pathway in the liver. In different mouse models bearing an activated beta-catenin signaling in the liver known to be associated with hepatocellular proliferation we observed a marked up-regulation of these three genes. The cellular distribution of GS and GLT-1 parallels beta-catenin activity. By contrast no up-regulation of these three genes was observed in the liver in which hepatocyte proliferation was induced by a signal-independent of beta-catenin. In addition, the GS promoter was activated in the liver of GS(+/LacZ) mice by adenovirus vector-mediated beta-catenin overexpression. Strikingly, the overexpression of the GS gene in human HCC samples was strongly correlated with beta-catenin activation. Together, our results indicate that GS is a target of the Wnt/beta-catenin pathway in the liver. Because a linkage of the glutamine pathway to hepatocarcinogenesis has already been demonstrated, we propose that regulation of these three genes of glutamine metabolism by beta-catenin is a contributing factor to liver carcinogenesis.
pubmed:language
eng
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:author
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
8293-301
pubmed:dateRevised
2006-11-15
pubmed:articleTitle
New targets of beta-catenin signaling in the liver are involved in the glutamine metabolism.
pubmed:affiliation
Département de Génétique, Développement et Pathologie Moléculaire, Institut Cochin, (INSERM U567, CNRS UMR 8104, Université Paris V), 24 rue du Faubourg St-Jacques, 75014 Paris, France.