2007 Fiscal Year Final Research Report Summary
Therapeutic application of c-myc gene transcriptional repressor via its apoptotic function for cancer treatment
| Project/Area Number |
18591453
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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 |
MATSUSHITA Kazuyuki Chiba University, HOSPITAL, EMERGENCY AND CRITICAL CARE MEDICINE, ASSISTANT PROFESSOR (90344994)
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| Co-Investigator(Kenkyū-buntansha) |
TOMONAGA Takeshi CHIBA UNIVERSITY, GRADUATE SCHOOL OF MEDICIE, MOLECULAR DIAGNOSIS, ASSOCIATE PROFESSOR (80227644)
SHIMADA Hideaki CHIBA UNIVERSITY, GRADUATE SCHOOL OF MEDICIE, FRONTIER SURGERY, ASSOCIATE PROFESSOR (20292691)
NOMURA Fumio CHIBA UNIVERSITY, GRADUATE SCHOOL OF MEDICIE, MOLECULAR DIAGNOSIS, PROFESSOR (80164739)
MATSUBARA Hisahiro CHIBA UNIVERSITY, GRADUATE SCHOOL OF MEDICIE, FRONTIER SURGERY, PROFESSOR (20282486)
NISHIMORI Takanori CHIBA UNIVERSITY, HOSPITAL, FRONTIER SURGERY, ASSISTANT PROFESSOR (30401003)
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| Project Period (FY) |
2006 – 2007
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| Keywords | apoptosis / cancer gene therapy / c-myc gene / transcriptional factor / cancer treatment |
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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, 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 to sustain high levels of c-Myc and oppose apoptosis in colorectal cancer.
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