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Down-modulation of EGF receptor by Interferon

干扰素下调 EGF 受体

基本信息

批准号：
03807013
负责人：
KARASAKI Yuji
金额：
$ 1.22万
依托单位：
Univ.of Occ.&Env.Health, Sch of Med.
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1991
资助国家：
日本
起止时间：
1991 至 1993
项目状态：
已结题

项目摘要

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.

在相同的培养条件下，IFN-γ对表皮生长因子（EGF）受体结合和正常和猿猴病毒40（SV 40）转化的人成纤维细胞的细胞生长的影响进行了比较。IFN-γ可增强EGF与正常细胞的结合，而降低EGF与SV 40转化细胞的结合。10 u/ml的IFN-γ作用72 h后，对正常细胞的刺激作用达到半最大，在10^2 u/ml的IFN-γ作用72 h后，刺激作用达到最大。当IFN-γ浓度低于10 u/ml时，SV 40转化细胞72 h的半数最大减少量为100 μ g/ml，当IFN-γ浓度为103 μ g/ml时，SV 40转化细胞72 h的半数最大减少量为100 μ g/ml，72小时。Scatchard分析表明，正常细胞和SV 40转化细胞的EGF结合位点数分别为1.6 × 0^5个/细胞和1.7 × 10^5个/细胞，IFN-γ处理几乎没有改变。然而，正常细胞的解离常数（k_d）从4.5 nM（对照）降低到2.0 nM（IFN处理），而SV 40转化细胞的k_d从0.67 nM（对照）增加到2.0 nM（IFN处理）。EGF可促进正常细胞DNA合成，IFN-γ处理可增强EGF对DNA合成的影响，可能与EGF与细胞的亲和力增加有关。另一方面，IFN-γ抑制转化细胞的DNA合成和增殖。上述对比结果表明，SV 40转化可能引起细胞膜结构的改变，IFN-γ处理可能诱导EGF受体的差异调节。