Down-regulation of c-myc mRNA after completion of liver regeneration in transgenic mice expressing hepatocyte growth factor in liver.

Hepatocyte growth factor (HGF) is the potent mitogen for liver parenchymal cells. It has been demonstrated that HGF enhances liver regeneration in transgenic mice which express HGF highly and exclusively in hepatocytes. In HGF transgenic mice where DNA synthesis of hepatocytes is active, c-myc is induced through an increased transcription rate by HGF. Therefore, expression of c-myc is up-regulated by HGF in this condition. However, relations between c-myc, HGF and cell growth still remain unclear. To clarify regulatory mechanisms of c-myc, we measured c-myc mRNA, HGF mRNA, proliferating nuclear antigen (PCNA) mRNA, PCNA protein and labeling index after a two thirds partial hepatectomy in livers from transgenic mice which express HGF in liver. We found that expression of c-myc mRNA was high on day 1 and day 3, and decreased drastically on day 5 when liver regeneration had completed in HGF transgenic mice (Shiota, et al., 1994). Levels of PCNA protein and labeling index on day 1 after liver regeneration were higher in HGF transgenic mice than those of normal siblings, but no differences were observed between HGF transgenic and wild type ]nice on day 3. Endogenous expression of HGF was observed only on day 1, although transgene expression was almost constant during liver regeneration. These data suggest that cell-to-cell contact is more important for regulation of c-myc than levels of HGF mRNA.