1997 Fiscal Year Final Research Report Summary
Association of gastrointestinal cancer progression and the alteration of cancer related genes.
| 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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| Keywords | Colon cancer / genetic instability / E2F-4 / MSH3 |
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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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[Publications] Ikeda, M., Orimo, H., Moriyama, H., Nakajima, E., Matsubara, N., Mibu, R., Tanaka, N.Shimada, T., Kimura, A., and Shimizu, K.: "Close correlation between mutations of E2F-4 and hMSH3 genes in colorectal cancers with microsatellite instability." Cancer Res.58 (in press). (1998)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Souza, R.F., Yin, J., Smolinski, K.N., Zou, T-T., Wang, S., Shi, Y-Q., Rhyu, M-G., Cottrell, J., Abraham, J.M., Biden, K., Simms, L., Leggett, B., Bova, G.S., Frank, T., Powell, S.M., Sugimura, H., Young, J., Harpaz, N., Shimizu, K., Matsubara, N., Meltzer, S.J.: "Frequent mutation of the E2F-4 cell cycle gene in primary human gastrointestinal tumors." Cancer Res.57. 2350-2353 (1997)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Matsubara.N., Yoshitaka, T., Ikeda, M., Takashima, H., Tanaka, N., and Shimizu, K.: "E2F-4 trinucleotide repeats is a target of microsatellite instability in human colorectal cancer but not in gastric cancer. (Meeting abstract)." Proc.Annu.Meet.Am.Assoc.Cancer Res.38. A2401 (1997)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Souza, R.F., Yin, J., Smolinski, K.N., Wang, S., Zou, T-T., Abraham, J.M., Powell, S.M., Sugimura, H., Matsubara, N., and Meltzer, S.J: "Mutant in a coding region of E2F-4 in genetically unstable gastic tumors. (Meeting abstract)." Proc.Annu.Meet.Am.Assoc.Cancer Res.38. A2400 (1997)
Description
「研究成果報告書概要(欧文)」より
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[Publications] RF Souza, J Yin, KN Smolinski, S Wang, T-T Zou, JM Abraham, K Biden, L Simms, B Leggett, K Shimizu, SM Powell, H Sugimura, N Harpaz, J Young, N Matsubara and SJ Meltzer: "Mutation of a coding region microsatelite within E2F-4 in genetically unstable gastrointestinal tumors. (Meeting abtract)" Gastrointestinal Oncology AGA Research Forum. Digestive Disease Week.A1629 (1997)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Yoshitaka, T., Matsubara.N., Ikeda, M., Tanino, M., Hanafusa, H., Tanaka, N., and Shimizu, K.: "Mutation of E2F-4 trinucleotide repeats in coloerctal cancer with microsatellite instability." Biochem.Biophys.Res.Commun.227. 553-557 (1996)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Matsubara, N., Hietala, O.A., Gilmore, S.K., Yum., K.Y., Litwin, S., Watts., P., Brennan, E.F., O'Brien, T.G.: "Association between high levels of ornithine decaboxylase activity and favorable prognosis in human colorectal carcinoma." Clinical Cancer Research. 1. 665-671 (1995)
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「研究成果報告書概要(欧文)」より
