Linked Life Data

11280770

Source:http://linkedlifedata.com/resource/pubmed/id/11280770

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2001-3-30
pubmed:abstractText
Mutations affecting phosphorylation sites in the beta-catenin gene have been implicated in the development of human and rodent hepatocellular carcinomas (HCCs). To further investigate the involvement of this gene in hepatocarcinogenesis, we used several transgenic mouse models of hepatic tumors induced by overexpression of c-myc in the liver either alone or in combination with transforming growth factor (TGF) alpha or TGF-beta1. Activation of beta-catenin, as judged by the presence of mutations and/or nuclear translocation of the protein, was most frequent in liver tumors from c-myc (4/17; 23.5%) and c-myc/TGF-beta1 (6/18; 33.3%) transgenic mice. However, it was very rare in faster growing and histologically more aggressive HCCs developed in c-myc/TGF-alpha mice (1/20; 5%). Administration of diethylnitrosamine, phenobarbital, or 2-amino-3,8-diethylimidazo[4,5-f]quinoxaline did not significantly affect the occurrence of beta-catenin mutations. Notably, nuclear accumulation of beta-catenin was observed only in adenomas and highly differentiated carcinomas with eosinophilic phenotype. Furthermore, preneoplastic lesions with eosinophilic phenotype frequently displayed focal nuclear positivity, colocalized with areas of high proliferation. In contrast, basophilic and clear-cell foci, as well as pseudo-glandular and poorly differentiated HCCs, exhibited a normal or reduced membranous immunoreactivity for beta-catenin. These studies suggest that nuclear translocation of beta-catenin and activation of Wingless/Wnt signaling may represent an early event in liver carcinogenesis, providing a growth advantage in a subset of hepatic tumors with a more differentiated phenotype.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
61
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2085-91
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:11280770-Animals, pubmed-meshheading:11280770-Cytoskeletal Proteins, pubmed-meshheading:11280770-Gene Expression Regulation, Neoplastic, pubmed-meshheading:11280770-Genes, myc, pubmed-meshheading:11280770-Humans, pubmed-meshheading:11280770-Immunohistochemistry, pubmed-meshheading:11280770-Liver Neoplasms, Experimental, pubmed-meshheading:11280770-Mice, pubmed-meshheading:11280770-Mice, Inbred BALB C, pubmed-meshheading:11280770-Mice, Inbred C57BL, pubmed-meshheading:11280770-Mice, Inbred CBA, pubmed-meshheading:11280770-Mice, Transgenic, pubmed-meshheading:11280770-Phenotype, pubmed-meshheading:11280770-Phosphorylation, pubmed-meshheading:11280770-Proto-Oncogene Proteins c-myc, pubmed-meshheading:11280770-Trans-Activators, pubmed-meshheading:11280770-Transforming Growth Factor alpha, pubmed-meshheading:11280770-Tumor Cells, Cultured, pubmed-meshheading:11280770-beta Catenin
pubmed:year
2001
pubmed:articleTitle
Activation of beta-catenin during hepatocarcinogenesis in transgenic mouse models: relationship to phenotype and tumor grade.
pubmed:affiliation
Division of Basic Sciences, National Cancer Institute, NIH, Bethesda, Maryland 20892-4255, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't