| Project/Area Number |
16591292
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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 | Chiba University |
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Principal Investigator |
MATSUZHITA Kazuyuki CHIBA UNIVERSITY, HOSPITAL, RESEARCH ASSISTANT, 医学部附属病院, 助手 (90344994)
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| Co-Investigator(Kenkyū-buntansha) |
TOMONAGA Takeshi CHIBA UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, ASSOCIATE PROFESSOR, 大学院・医学研究院, 助教授 (80227644)
SHIMADA Hideaki CHIBA UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, ASSISTANT PROFESSOR, 大学院・医学研究院, 講師 (20292691)
MATSUBARA Hisahiro CHIBA UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, ASSISTANT PROFESSOR, 大学院・医学研究院, 講師 (20282486)
NOMURA Fumio CHIBA UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, PROFESSOR, 大学院・医学研究院, 教授 (80164739)
OCHIAI Takenori CHIBA UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, PROFESSOR, 大学院・医学研究院, 教授 (80114255)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | c-myc gene / Transcriptional repressor / alternative splicing variats / cancer gene therapy / apotosis / 癌治療 |
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| Research Abstract |
Elevated expression of c-myc has been detected in a broad range of human cancers, indicating a key role for this oncogene in tumor development. Recently, an interaction between FIR (FBP Interacting Repressor) and TFIIH/p89/XPB helicase was found to repress c-myc transcription and so might be important for suppressing tumor formation. In this study, we showed that enforced expression of FIR induced apoptosis. Deletion of FIR's amino terminal repression domain rescued the cells from apoptosis, as did co-expression of c-Myc with FIR ; thus repression of Myc mediates FIR-driven apoptosis. Surprisingly, a splicing variant of FIR unable to repress c-myc nor to drive apoptosis was frequently discovered in human primary colorectal cancers, but not in the adjacent normal tissues. Coexpression of this splicing variant with repressor-competent FIR, either in HeLa cells or in the colon cancer cell line SW480,not only abrogated c-Myc suppression but inhibited apoptosis. These results strongly suggest the expression of this splicing variant promotes tumor development by disabling FIR-repression and so sustaining high levels of c-Myc and opposing apoptosis in colorectal cancer. One route to the development of cancer therapies directed against c-Myc may go through FIR and its variants
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