| Project/Area Number |
09672360
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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 |
Laboratory medicine
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| Research Institution | Nagasaki University |
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Principal Investigator |
KAMIHIRA Shimeru Laboratory Medicine, Nagasaki University, Professor, 医学部, 教授 (80108290)
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| Co-Investigator(Kenkyū-buntansha) |
MAEDA Takahiro Dept. of Hematology, Nagasaki University, Assistant Professor, 医学部, 助手 (40284674)
YAMADA Yasuaki Laboratory Medicine, Nagasaki University, Associate Professor, 医学部, 助教授 (60145232)
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| Project Period (FY) |
1997 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1998: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1997: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | Fas / isoform / ATL / HTLV-I / tumorigenesis / Apoptosis / Fas ligand / mutation / AIDS / isofarm / HTLV-I / Aios |
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| Research Abstract |
The Fas-Fas ligand signal transduction system is well known to be involved in not only normal development but also incurable disorders, such as neoplasms and immune-diseases. There are possible three factors in terms of tumorigensis via Fas receptor; 1) down-regulation of membrane (m) Fas to escape from tumor elimination, 2)dominat negative action due to mutated Fas, and 3)inhibitory or antagonistic function by isoform of soluble(s) Fas. To address each issue described above, we studied the relationship between expression of aberrant Fas isoforms and ATL cell biology. First of all, quantitative flow cytometric assay revealed that 90% ATL had tumor cells up-regulating mFas, while l0% ATL had cells negative for mFas with no mutated Fas genes (Br J Haematol 99;858,1997). Secondly, we encountered a case with mFas positive ATL cells of which no signal transduction via Fas receptor was evident, Molecular analysis on these cells revealed mutated Fas deleting 20bp at exon 9 and resulting in truncated Fas proteins. This truncated Fas was evident to serve as dominant negative function in the experimental system of Jurkat cell line transfected with the gene (J Exp Med 189:1063,1999). Thirdly, our study also disclosed a possible mechanism which over-productive sFas acts as decoy function to prevent from cell death via the Fas-FasL signal system (Br J Haematol 107;851, 1999).
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