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 mR NA and protein, beginning prior to peak. DNA synthesis. In normal rat liver, basal levels of cyclin D1 protein were significantly higher tha n in the mouse. After hepatectomy in the rat, cyclin D1 mRNA was induc ed 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 fresh ly isolated rat hepatocytes, but this diminished within 6 hours in cul ture. After growth stimulation with HGF, cyclin D1 mRNA was induced 3- to 5-fold and its protein >20-fold in rat hepatocytes. Immunoprecipit ation of cyclin D1 demonstrated its association with cdk4 but not cdk5 in regenerating liver. In human liver biopsy specimens, cyclin D1 pro tein was detectable in normal liver and induced 2- to 10-fold in mitot ically active liver following transplantation. These results suggest t hat the regulation of cyclin D1 protein in human liver may more closel y parallel the mouse than the rat hepatectomy model. Furthermore, cycl in expression in primary cells in culture may differ significantly fro m that observed in vivo. (C) 1995 Academic Press, Inc.