Wang D, Yang E B, Cheng L Y
Department of Biochemistry, Faculty of Medicine, National University of Singapore, Singapore.
Anticancer Res. 1996 Sep-Oct;16(5A):3001-6.
TNF alpha is known to exert multi-regulatory effects on normal and malignant cell functions by binding to the corresponding cell surface receptor. However, the existence of cross interaction between TNF alpha and EGF receptor has been proposed. In this study, we investigated the modulatory effect of TNF alpha on EGF receptor of a human hepatocellular carcinoma cell line-HepG2. The results suggested that TNF alpha was able to modulate the EGF receptor of HepG2 cells. The modulatory effect of TNF alpha on the EGF receptor of HepG2 cells exhibited its unique characteristics in comparison with the previous reports on other tumor 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 alpha was also able to reduce the affinity of the high-affinity receptor for EGF. However, there was no significant alteration in terms of the expression of EGF receptor, EGF internalization, or EGF degradation when HepG2 cells were treated with TNF alpha. Since TNF alpha is an inhibitory agent for HepG2 cell growth, this cross interaction between TNF alpha and EGF receptor may play a role in the inhibition of cell growth.
已知肿瘤坏死因子α（TNFα）通过与相应的细胞表面受体结合，对正常细胞和恶性细胞功能发挥多种调节作用。然而，有人提出TNFα与表皮生长因子（EGF）受体之间存在交叉相互作用。在本研究中，我们调查了TNFα对人肝癌细胞系HepG2的EGF受体的调节作用。结果表明，TNFα能够调节HepG2细胞的EGF受体。与先前关于其他肿瘤细胞的报道相比，TNFα对HepG2细胞EGF受体的调节作用表现出其独特的特征。TNFα还能增强HepG2细胞EGF受体的酪氨酸磷酸化。然而，这种作用仅在存在EGF时才出现，并非由TNFα单独介导。因此，TNFα对HepG2细胞EGF受体酪氨酸磷酸化的作用是由于增强了受体对EGF的反应。TNFα还能够降低高亲和力受体对EGF的亲和力。然而，用TNFα处理HepG2细胞时，EGF受体的表达、EGF内化或EGF降解方面均无显著改变。由于TNFα是HepG2细胞生长的抑制剂，TNFα与EGF受体之间的这种交叉相互作用可能在细胞生长抑制中发挥作用。
