[Changes in the epidermal growth factor receptors in the liver cells of rats in N-nitrosodiethylamine-induced hepatic carcinogenesis].

A sharp decrease in the number of epidermal growth factor receptors (EGF-R) in the rat liver plasma membranes had been found at different stages of diethylnitrosamine-induced carcinogenesis. The complete loss of high-affinity binding sites for EGF did not prevent EGF-dependent autophosphorylation of EGF-R. Hepatocytes from the rat liver tumors in the primary culture had two classes of EGF-R: high and low affinity ones, though their number had been twice less than in the normal hepatocytes. The dynamics of internalization and down-regulation of EGF-R was very similar in the primary culture of transformed and normal hepatocytes. It testifies that there are some factors of microenvironment in the liver during carcinogenesis which cause the loss of EGF-R (down-regulation) and a decrease of their affinity (activation of protein kinase C). A possible autocrine or paracrine nature of these factors is discussed.