Linked Life Data

17006939

Source:http://linkedlifedata.com/resource/pubmed/id/17006939

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2006-10-3
pubmed:abstractText
Hepatocyte growth factor (HGF) and beta-catenin both play a crucial role in stimulating hepatocyte proliferation, but whether these 2 pathways cooperate in inducing hepatocyte proliferation is unclear. We have previously reported that beta-catenin forms a complex with c-Met (HGF receptor) that undergoes dissociation because of beta-catenin tyrosine phosphorylation on stimulation by HGF. It is also known that delivery of the human HGF gene cloned in a plasmid under a CMV promoter results in hepatomegaly in mice. In addition, recently characterized beta-catenin transgenic mice also showed hepatomegaly. The present study was based on the hypothesis that HGF-induced hepatomegaly is mediated, at least in part, by activation of the Wnt/beta-catenin pathway. Here we report that delivery of the human HGF gene delivery in mice led to hepatomegaly via beta-catenin activation in the liver in 1- and 4-week studies. The mechanisms of beta-catenin activation in the 1-week study included loss of c-Met-beta-catenin association as well as canonical beta-catenin activation, leading to its nuclear translocation. In the 4-week study, beta-catenin activation was observed via canonical mechanisms, whereas the c-Met-beta-catenin complex remained unchanged. In both studies there was an associated increase in the E-cadherin-beta-catenin association at the membrane. In addition, we generated liver-specific beta-catenin knockout mice, which demonstrated significantly smaller livers. HGF gene delivery failed to induce hepatomegaly in these beta-catenin conditionally null mice. In conclusion, beta-catenin- and HGF-mediated signaling pathways cooperate in hepatocyte proliferation, which may be crucial in liver development, regeneration following partial hepatectomy, and pathogenesis of hepatocellular carcinoma.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0270-9139
pubmed:author
pubmed:issnType
Print
pubmed:volume
44
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
992-1002
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Activation of Wnt/beta-catenin pathway during hepatocyte growth factor-induced hepatomegaly in mice.
pubmed:affiliation
Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15216, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural