| Project/Area Number |
11671237
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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 | Okayama University |
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Principal Investigator |
TANAKA Noriaki Okayama University, Graduate School of Medicine and Dentistry, Professor, 大学院・医歯学総合研究科, 教授 (10127566)
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| Co-Investigator(Kenkyū-buntansha) |
SHIMIZU Kenji Okayama University, Graduate School of Medicine and Dentistry, Professor, 大学院・医歯学総合研究科, 教授 (10037286)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1999: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | colon cancer / genetic instability / E2F-4 / chemosensitivity / 大腸癌 / 化学療法 |
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| Research Abstract |
E2F is a family of transcription factors implicated in the regulation of gene expression required for progression through the G1-S transition. We have previously detected tumor-specific mutations at a trinucleotide repeat coding sequence of E2F-4 gene in a subset of human sporadic colorectal cancers. The purpose of this study was to investigate the potential functional consequences of these E2F-4 mutations. We transfected NIH3T3 fibroblasts with expression constructs containing wild type as well as mutant E2F-4 cDNA and the effect of the E2F-4 mutations on proliferation was examined. Alteration in transactivation of the E2F consensus promoter sequence was also examined by transient cotransfection of a E2F-4 with a DP-2 construct into cultured human cells. Transfected cell clones overexpressing mutant E2F-4 grew more rapidly and showed higher proliferative activity by increased immunohistochemical staining for proliferating cell nuclear antigen (PCNA). All three mutant forms of E2F-4 showed elevated transactivation of the E2F consensus promoter sequence. Thus, expression of mutant E2F-4s confers a growth advantage in vivo, and this effect may be related to the acquisition of a neoplastic phenotype.
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