Distinct patterns of cyclin D1 regulation in models of liver regeneration and human liver.

The expression of cyclin D1 and associated cdks was examined in models of liver regeneration and human liver specimens. In mouse liver after 70% partial hepatectomy, there was > 20-fold induction of cyclin D1 mRNA and protein, beginning prior to peak DNA synthesis. In normal rat liver, basal levels of cyclin D1 protein were significantly higher than in the mouse. After hepatectomy in the rat, cyclin D1 mRNA was induced 6- to 10-fold, while the protein levels changed < 2-fold and did not parallel changes in the mRNA. Cyclin D1 protein was detected in freshly isolated rat hepatocytes, but this diminished within 6 hours in culture. After growth stimulation with HGF, cyclin D1 mRNA was induced 3- to 5-fold and its protein > 20-fold in rat hepatocytes. Immunoprecipitation of cyclin D1 demonstrated its association with cdk4 but not cdk5 in regenerating liver. In human liver biopsy specimens, cyclin D1 protein was detectable in normal liver and induced 2- to 10-fold in mitotically active liver following transplantation. These results suggest that the regulation of cyclin D1 protein in human liver may more closely parallel the mouse than the rat hepatectomy model. Furthermore, cyclin expression in primary cells in culture may differ significantly from that observed in vivo.