Hepatocyte growth factor (HGF) increased both levels of phosphorylated and non-phosphorylated forms of retinoblastoma protein (RB) in primary cultured rat hepatocytes. Combined treatment of HGF and a specific inhibitor of ornithine decarboxylase (ODC), alpha-difluoromethylornithine (DFMO), reduced the levels of hyper-phosphorylated and hypo-phosphorylated forms of RB and increased the levels of the non-phosphorylated form, compared to HGF alone, but did not affect the total level of RB. Polyamines added exogenously overcame the effects of DFMO; they increased hyper- and hypo-phosphorylated forms and decreased non-phosphorylated RB. TGF-beta1 inhibited the increases in ODC activity, RB phosphorylation, and DNA synthesis induced by HGF. However, polyamines added exogenously could not overcome the inhibition by RB phosphorylation and DNA synthesis by TGF-beta1. These results suggest that polyamines are involved in the phosphorylation of RB, but the inhibition of polyamine biosynthesis by TGF-beta1 did not result in the inhibition of RB phosphorylation and DNA synthesis.
Copyright 1998 Academic Press.