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.