Changes in WNT/beta-catenin pathway during regulated growth in rat liver regeneration.
The wnt/beta-catenin pathway is important during embryogenesis and carcinogenesis. beta-Catenin interaction with E-cadherin has been shown to be crucial in cell-cell adhesion. We report novel findings in the wnt pathway during rat liver regeneration after 70% partial hepatectomy using Western blot analyses, immunoprecipitation studies, and immunofluorescence. We found wnt-1 and beta-catenin proteins to be predominantly localized in hepatocytes. Immediately following partial hepatectomy, we observed an initial increase in beta-catenin protein during the first 5 minutes with its translocation to the nucleus. We show this increase to be the result of decreased degradation of beta-catenin (decrease in serine phosphorylated beta-catenin) as seen by immunoprecipitation studies. We observed activation of beta-catenin degradation complex comprising of adenomatous polyposis coli gene product (APC) and serine-phosphorylated axin protein, beginning at 5 minutes after hepatectomy, leading to its decreased levels after this time. Quantitative changes observed in E-cadherin protein during liver regeneration are, in general, reverse to those seen in beta-catenin. In addition, using immunoprecipitation, we observe elevated levels of tyrosine-phosphorylated beta-catenin at 6 hours onward. Thus, changes in the wnt pathway during regulated growth seem to tightly regulate cytosolic beta-catenin levels and may be contributing to induce cell proliferation and target gene expression. Furthermore, these changes might also be intended to negatively regulate cell-cell adhesion for structural reorganization during the process of liver regeneration.
Monga
S P
SP
Department of Pathology, University of Pittsburgh, School of Medicine, PA, USA.
Pediaditakis
P
P
Mule
K
K
Stolz
D B
DB
Michalopoulos
G K
GK
D000818:Animals; D060466:Axin Protein; D001692:Biological Transport / Q000502:physiology; D015820:Cadherins / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D010766:Phosphorylation; D011506:Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D012016:Reference Values; D012097:Repressor Proteins; D013997:Time Factors; D014018:Tissue Distribution; D015534:Trans-Activators; D014443:Tyrosine / Q000378:metabolism; D051153:Wnt Proteins; D051155:Wnt1 Protein; D029961:Zebrafish Proteins; D051176:beta Catenin
D060466:Axin Protein; D015820:Cadherins; C495268:Ctnnb1 protein, rat; D003598:Cytoskeletal Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D051153:Wnt Proteins; D051155:Wnt1 Protein; C495245:Wnt1 protein, rat; D029961:Zebrafish Proteins; D051176:beta Catenin; D014443:Tyrosine