| Project/Area Number |
07671306
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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 |
General surgery
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| Research Institution | Okayama University |
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Principal Investigator |
GOUCHI Akira Okayama University Medical School, First Department of Surgery, instructor, 医学部・附属病院, 助手 (10186877)
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| Co-Investigator(Kenkyū-buntansha) |
松原 長秀 岡山大学, 医学部・附属病院, 医員
SHIMIZU Kenji Okayama University Medical School, First Department of Surgery, Professor, 医学部, 教授 (10037286)
TANAKA Noriaki Okayama University Medical School, First Department of Surgery, Professor, 医学部, 教授 (10127566)
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| Project Period (FY) |
1995 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1997: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1996: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1995: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | Colon cancer / genetic instability / E2F-4 / MSH3 / 大腸癌 / DNA修復異常 / microsatellite instability / CAG繰り返し配列 / ornihine decarboxylase (0DC) / 癌悪性化機構 / 遺伝子不安定化 / 遺伝子複製異常 |
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| Research Abstract |
The E2F group of transcription factors transactivates genes that promote progression through the G1-S transition of the cell cycle. Members of the retinoblastoma (Rb) family of proteins bind to E2Fs and inhibit this function. E2F-4, one example of the E2F group, functions as an oncogene when transfected into nontransformed cell in vitro. On the other hand, mice that are homozygously lacking a normal E2F-1 gene develop cancers, cosistent with a tumor-suppressive role for this gene. The exact function of E2Fs has thus been unclear ; moreover, direct invlvement of this gene in primary human tumorigensis has not been shown.
Defects in mispatch repair function can lead to the microsateillite instability (MI) phenotype in certain human cancers. We have identified E2F-4 having frequent tumor-specific mutations at the trinucleotide coding microsatellite (CAG repeats) in a subset of human sporadic CRC with MI phenotype. We also found a relatively high rate of mutation within E2F-4 in gastric cancer and ulcerative colitis related tumor with MI.
Additional investigations revealed that somatic mutation in E2F-4 gene are closely associtated with defects in the hMSH3 gene and are possibly selected during the progression of colorectal MI tumors.
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