Additivity of the proliferative effects of HGF/SF and EGF on hepatocytes

The additivity of DNA synthesis induced by hepatocyte growth factor/scatter factor (HGF/SF) and epidermal growth factor (EGF) was revealed in periport al hepatocytes (PPH), perivenous hepatocytes (PVH), and primary hepatocytes . Furthermore, additivity of the signal transduction pathway of HGF/SF and EGF was investigated (i.e., the activity of mitogen-activated protein kinas e (MAPK) induced by HGF/SF and EGF), but it was not seen in PPH, PVH, or pr imary hepatocytes, although wortomannin, a PI 3-kinase inhibitor, abolished the additivity. The additivity of DNA synthesis induced by HGF/SF and EGF was not related to hepatocyte heterogeneity, but to a difference in the sig nal transduction pathway, probably another pathway that is different from t he classical MAPK (MAPK/ERK1,2) path, (C) 2000 Academic Press.