Down-modulation of EGF receptor by Interferon

点击翻译按钮获取中文摘要

The effects of IFN- on the epidermal growth factor(EGF) receptor binding and cell growth of normal and simian virus 40(SV40)- transformed human fibroblast cells were compared under identical culture conditions. IFN- induced an enhancement of EGF binding to the nomal cells, while it decreased the EGF binding to the SV40-transformed cells. Half-maximal enhancemant occurred at 72h after the normal cells were exposed to 10 u/ml of IFN- and maximal stimulation was obtained at about 10^2 u/ml of IFN- for 72h.On the other hand, the half-maximal reduction was observed for the SV40-transformed cells at less than 10 u/ml of IFN- for 72h and maximal reduction was obtained at around 10^3 u/ml of IFN- for 72h. Scatchard analysis indicated that the numbers of EGF binding sites of the normal and the SV40-transformed cells were calculated to be 1.6 X 0^5 per cell and 1.7 X 10^5 per cell, respectively and were little altered by the IFN- treatment. The dissociation constant(k_d) of the normal cells, however, decreased from 4.5 nM (control)to 2.0 nM(IFN- treated), while the k_d of the SV40- transformed cells increased from 0.67 nM(control) to 2.0 nM(IFN-treated). The DNA synthesis of the normal cells was enhanced by EGF and IFN- treatment potentiated the effect of EGF on the DNA synthesis, probably due to the increase of the affinity of EGF to the cells. On the other hand, IFN- reduced the DNA synthesis and prolifer-ation of the transformed cells. The above contrast results indicate that the SV40-transformation may cause alterations to the membrane structure of the cells and IFN- treatment might induce differential modulation of EGF receptors.