MODULATION OF EGF RECEPTOR BY TUMOR-NECROSIS-FACTOR-ALPHA IN HUMAN HEPATOCELLULAR-CARCINOMA HEPG2 CELLS

TNF alpha is known to exert multi-regulatory effects on normal and mal ignant cell functions by binding to the corresponding cell surface rec eptor. However; the existence of cross interaction between TNF alpha a nd EGF receptor has been proposed. In this study, we investigated the modulatory effect of TNF alpha on EGF receptor of a human hepatocellul ar carcinoma cell line - HepG2. The results suggested that TNF alpha w as able to modulate the EGF receptor of HepG2 cells. The modulatory ef fect of TNF alpha on the EGF receptor of HepG2 cells exhibited its uni que characteristics in comparison with the previous reports on other t umor cells. TNF alpha could also enhance the tyrosine phosphorylation of the EGF receptor of HepG2 cells. However; the effect appeared only if EGF was present, and was not mediated by TNF alpha alone. Therefore , the effect of TNF alpha on EGF receptor tyrosine phosphorylation in HepG2 cells was due to enhancing the receptor's response to EGF. TNF a lpha was also able to reduce the affinity of the high-affinity recepto r for EGF. However, there was no significant alteration in terms of th e expression of EGF receptor, EGF internalization or EGF degradation w hen HepG2 cells were treated with TNF alpha. Since TNF alpha is an inh ibitory agent for HepG2 cell growth, this cross interaction between TN F alpha and EGF receptor may play a role in the inhibition of cell gro wth.