1997 Fiscal Year Final Research Report Summary
Cell Killing effect heparin-binding EGF-like growth factor
| Project/Area Number |
07670553
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | ASAHIKAWA MEDICAL COLLEGE |
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Principal Investigator |
ONO Minoru Asahikawa medical college Lecturer, 医学部, 講師 (60185650)
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| Project Period (FY) |
1995 – 1997
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| Keywords | HBEGF / Heparin / Tunror / Hepatoma / tokim / growth / chemotherapy / Pseudomonas |
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| Research Abstract |
Heparin-binding EGF-like growth factor (HB-EGF) is a potent mitogen for smooth muscle cell, fibroblast, and it also stimulates hepatocyte proliferation. We generated several chimeric toxins by fusing the cDNA sequence of HB-EGF and the mutant of Pseudomonas exotoxin, PE^<4E>KDEL (PE) that lacks the binding abiliy to specific receptor. HB-EGF-PE was generated by fusing the DNA fragment encoding the full length mature HB-EGF polypeptide to the N-terminus of PE^<4E>KDEL,while HB-PE was generated by fusing the 45 N-terminal heparin-binding sequence to PE^<4E>KDEL.HB-EGF-PE was capable of binding both to EGF receptor and heparan sulfate proteoglycans (HSPGs), whereas HB-PE was capable of binding only to HSPGs on the target cells. Human hepatoma cells, SK-Hep1, Hep-G2 and PLC/PRF/5 were killed in a very low concentration of HB-EGF-PE with the ID50 of 0.1 to 0.5 ng/ml. HB-PE could also killed SK-Hep1 with the ID50 of 50 ng/ml, whereas it was resistant to PE.Both exogenous EGF and heparin inhibited the cytotoxicity of HB-EGF-PE.These results indicated the existence of two alternative pathways for the internalization of the chimeric toxins defined by two different targets, EGFR and HSPGs.
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Research Products
(16 results)
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[Publications] Ayabe T,Ashida T,Taniguchi M,Nomura M,Einami K,Taruishi M,Saitoh Y,Santos SB,Ono M,Shibata Y,Kohgo Y.: "A pilot study of centrifugal leukocyte apheresis for cortocosteroid-resistant active ulcerative colitis." Int Med. 36. 322-326 (1997)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Mizukami Y,Ohhira M,Matsumoto A,Murazumi Y,Murazumi K,Ohta H,Ohhira Ma, Ono M,Miyake T,Maekawa I,Kohgo Y.: "Primary biliary cirrhosis associated with idiopatic thrombocytopenic purpura." J Gastroenterol. 31. 284-288 (1996)
Description
「研究成果報告書概要(欧文)」より
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