RAT-LIVER PLASMA-MEMBRANE ENHANCES INDUCTION OF DNA-SYNTHESIS BY EPIDERMAL GROWTH-FACTOR AND INSULIN IN CULTURED RAT HEPATOCYTES

DNA synthesis in rat hepatocytes in primary culture was induced by epidermal growth factor (EGF) and insulin added 24 h after plating. When rat liver plasma membrane (PM) was add-ed 30 h or 38 h after plating to the medium of this culture, DNA synthesis 50 h after plating was significantly increased compared to that in controls. The enhancement was markedly reduced when EGF and insulin were removed from the medium immediately before the PM addition. This stimulatory activity of PM was lost or markedly reduced when PM had been treated with heat, acid, trypsin, or bacterial collagenase. However, the stimulatory activity was detected in the supernatant from the collagenase-treated PM, in a fraction containing components with molecular weight lower than 25 K. These results indicate that PM contains a stimulatory factor for hepatocyte proliferation which acts as a comitogen of EGF and insulin. The factor is presumed to be a protein in character.