| Project/Area Number |
08671488
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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 |
Digestive surgery
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| Research Institution | TOHO UNIVERSITY |
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Principal Investigator |
HEMMI Hiromichi Toho Univ Sch Med, Dept Mol Biol, Assoc Prof, 医学部, 助教授 (90165514)
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| Co-Investigator(Kenkyū-buntansha) |
TSUJITA Kazunori Toho Univ Sch Med, 1st Dept Surg, Associate Prof, 医学部, 助教授 (60130374)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1997: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1996: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | mismatch repair genes / hMLH1 protein / hMSH2 protein / RER / microsatellite instability / target genes / TGF-beta signaling pathway / BAX gene / hMLHタンパク / hMLH1遺伝子 / TGF-βRII遺伝子 / IGFIIR遺伝子 |
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| Research Abstract |
(1) Expression of mismatch repair proteins, hMSH2 and hMLHl Expression of hMSH2 and hMLH1 proteins in 99 samples of sporadic colorectal cancer selected ramdomly was analyzed by Western blot with monoclonal antibodies developed in our laboratory. Totally 11 samples with no/little expressing hMSH2 (6 samples) and hMLH1 (5 samples) proteins in 99 tumor tissues were found, indicating approximately l0% of sporadic cases have some defects in the expression of these mismatch repair proteins.
(2) RER status To study RER status of the 90 sporadic cases, we selected 5 microsatellite markers. So far, l7 samples showing more than 2 loci of the microsatellite region of the 90 samples (l8.9%) were found. Ten of the 11 hMLH1- or hMSH2-defective samples showed RER phenotype.
(3) Mutation in microsatellite region of target genes To know the target genes, mutation in the microsatellite regions of the TGF-betaRII,IGFIIR,and BAX genes were studied. So far, mutation in one allele of the TGF-betaRII genes of the 15 RER samples was found.
(4) Future study lt is required to clarify the microsatellite markers for determining the RER status for Japanese patients, because there is no common microsatellite markers with high frequency for the detecting RER.Further specimens will be examined for RER status and mismatch repair system including candidates of target genes.
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