1993 Fiscal Year Final Research Report Summary
Down-modulation of EGF receptor by Interferon
| Project/Area Number |
03807013
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
General medical chemistry
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| Research Institution | Univ.of Occ.&Env.Health, Sch of Med. |
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Principal Investigator |
KARASAKI Yuji U.O.E.H.Dept.Biochem.Lecture, 医学部, 助手 (20140907)
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| Co-Investigator(Kenkyū-buntansha) |
GOTOH Sadao U.O.E.H.Dept.Biochem.Asso.Profes, 医学部, 助教授 (50131917)
HIGASHI Ken U.O.E.H.Dept.Biochem.Professor, 医学部, 教授 (30028386)
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| Project Period (FY) |
1991 – 1993
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| Keywords | Simian virus 40 / Interferon / Epidermal growth factor / sv40-トランスフォーム細胞 |
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| Research Abstract |
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.
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