Linked Life Data

12771026

Source:http://linkedlifedata.com/resource/pubmed/id/12771026

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2003-5-28
pubmed:abstractText
For growth stimulation of liver cells by hepatocyte growth factor (HGF) or transforming growth factor alpha (TGFalpha) via receptor tyrosine kinases, c-fos/c-jun has been considered a point of intersection for cross-talk between the different signal transduction pathways. Recent evidence strongly implicates translocation of pro-TGFalpha into the nucleus as an important step preceding the initiation of hepatic DNA synthesis. We asked whether an active c-jun is required for the nuclear translocation of pro-TGFalpha and its stimulatory effect on DNA synthesis. For this purpose we used mice with c-jun inactivated post partum in hepatocytes by the Cre-loxP recombination system (c-jun(Deltaliver)). Nuclear fractions from control and c-jun(Deltaliver) mouse livers contained TGFalpha as pro-form of 17 kDa and the epidermal growth factor receptor (erbb-1) with molecular weights of 170 and 150 kDa (truncated form). Hepatocytes were isolated by collagenase perfusion and cultivated. A lack of c-jun did not alter the apoptotic activity but significantly suppressed DNA synthesis in the cultured hepatocytes. In control and c-jun(Deltaliver) cells DNA synthesis was almost always associated with nuclear presence of pro-TGFalpha. 76.5 +/- 6.8% of hepatocytes with pro-TGFalpha positive nuclei and only 4.52 +/- 1.31% of hepatocytes with negative nuclei exhibited DNA replication. About 85% of the pro-TGFalpha positive nuclei also contained erbb-1. Treatment of cultures with mature TGFalpha or HGF elevated the frequency of pro-TGFalpha positive nuclei replicating DNA; HGF and TGFalpha-induced nuclear pro-TGFalpha and DNA synthesis significantly more in c-jun(Deltaliver) than in control hepatocytes. These results suggest that (i) a lack of c-jun suppresses basal rates of DNA replication in hepatocytes; (ii) c-jun deficient hepatocytes show a pronounced growth response towards HGF or TGFalpha; (iii) nuclear translocation of pro-TGFalpha together with erbb-1 and its association with DNA synthesis are independent of c-jun.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0143-3334
pubmed:author
pubmed:issnType
Print
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
835-41
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:12771026-Animals, pubmed-meshheading:12771026-Blotting, Southern, pubmed-meshheading:12771026-Cells, Cultured, pubmed-meshheading:12771026-DNA, pubmed-meshheading:12771026-DNA Replication, pubmed-meshheading:12771026-Electrophoresis, Gel, Two-Dimensional, pubmed-meshheading:12771026-Hepatocyte Growth Factor, pubmed-meshheading:12771026-Hepatocytes, pubmed-meshheading:12771026-Immunoblotting, pubmed-meshheading:12771026-Integrases, pubmed-meshheading:12771026-Liver, pubmed-meshheading:12771026-Male, pubmed-meshheading:12771026-Mice, pubmed-meshheading:12771026-Mice, Inbred C57BL, pubmed-meshheading:12771026-Mice, Knockout, pubmed-meshheading:12771026-Protein Precursors, pubmed-meshheading:12771026-Proto-Oncogene Proteins c-jun, pubmed-meshheading:12771026-Receptor, Epidermal Growth Factor, pubmed-meshheading:12771026-Recombination, Genetic, pubmed-meshheading:12771026-Transforming Growth Factor alpha, pubmed-meshheading:12771026-Viral Proteins
pubmed:year
2003
pubmed:articleTitle
Induction of DNA synthesis in primary mouse hepatocytes is associated with nuclear pro-transforming growth factor alpha and erbb-1 and is independent of c-jun.
pubmed:affiliation
Institut für Krebsforschung, University of Vienna, Borschkegasse 8a, Austria.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't