| Project/Area Number |
15590423
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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 |
Virology
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| Research Institution | Soka University |
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Principal Investigator |
TAKASE Sayaka Soka University, Department of Bioinformatics, Faculty of Engineering, Professor, 工学部生命情報工学科, 教授 (60236221)
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| Co-Investigator(Kenkyū-buntansha) |
WATANABE Rihito Soka University, Department of Bioinformatics, Faculty of Engineering, Professor, 工学部生命情報工学科, 教授 (30129746)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2003: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | Cancer / Thymoma / Tumorigenicity / LTR / Enhancer / c-myc / Retrovirus / Rat / 胸腺 / マウス白血病ウイルス |
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| Research Abstract |
Friend murine leukemia virus clone A8,which carries no oncogenes, causes thymoma 7 weeks post-infection in rats with a more rapid progression than clone 57. The U3 region of A8-LTR contains a unique structure of enhancer motifs consisting of three repeats of a 38-bp sequence containing FVa, LVb/C4, and CORE motifs. Replacement or deletion of the 38-bp sequence in the A8-U3 resulted in a marked reduction in tumorigenicity. Furthermore, the virus with 57-U3 gained high tumorigenicity after construction of the three 38-bp repeats in the U3 region. These findings indicated that the repeats of the 38-bp sequence of A8-LTR are essential for the rapid induction of thymoma. For retroviruses lacking viral oncogenes, proviral integration adjacent to proto-oncogenes of host cells, a phenomenon termed proviral insertional mutagenesis, plays a central role in tumor induction. Studies by genomic southern hybridization indicated that the viral gene was inserted into several specific positions of the host genome in thymoma of rat infected with A8 virus. However, in the thymus of rat infected with non-tumorigenic virus, the viral gene was inserted at random into the host genome. In thymoma, the expression level of mRNA of c-myc, which is an important proto-oncogene for tumorigenesis, was 3- to 8-fold higher compared with normal thymus. These results suggest that provirus insertion into specific positions of the host genome correlates with tumorigenesis by A8 virus infection and the overexpression of c-myc plays an important role.
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