| Project/Area Number |
12213001
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Hokkaido University |
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Principal Investigator |
TAKADA Kenzo Hokkaido Univ., Institute for Genetic Medicine, Prof., 遺伝子病制御研究所, 教授 (30133721)
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| Co-Investigator(Kenkyū-buntansha) |
KANNO Hiroyuki Institute for Genetic Medicine, Asso.Prof, 遺伝子病制御研究所, 助教授 (40252663)
丸尾 聖爾 北海道大学, 遺伝子病制御研究所, 助教授 (70292018)
NANBO Asuka Institute for Genetic Medicine, Lec., 遺伝子病制御研究所, 助手 (60359487)
IWAKIRI Dai Institute for Genetic Medicine, Lec., 遺伝子病制御研究所, 助手 (10307853)
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| Project Period (FY) |
2000 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥46,200,000 (Direct Cost: ¥46,200,000)
Fiscal Year 2004: ¥9,300,000 (Direct Cost: ¥9,300,000)
Fiscal Year 2003: ¥9,700,000 (Direct Cost: ¥9,700,000)
Fiscal Year 2002: ¥10,000,000 (Direct Cost: ¥10,000,000)
Fiscal Year 2001: ¥9,200,000 (Direct Cost: ¥9,200,000)
Fiscal Year 2000: ¥8,000,000 (Direct Cost: ¥8,000,000)
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| Keywords | Epstein-Barr Virus / Gastric Carcinoma / EBER / Growth Factor / Interferon / Apoptosis / small RNA / LMP2A / 上咽頭がん / IGF-1 / トランスフォーメーション / BARF1 / EBウィルス / CD21 / レセプター |
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| Research Abstract |
This project aimed at clarifying molecular mechanisms of gastric carcinoma induction by EBV, and obtained the following findings.
1. There are two distinct pathways in EBV infection of epithelial cells, a gp350-dependent pathway and a gp350-independent pathway, and gp25 can play a role in the infection of some epithelial cells.
2. EBV-encoded small RNA (EBER) binds interferon-inducible protein kinase, PKR, inhibits its phosphorylaltion, and confers resistance to FAS-mediated apoptosis in epithelial cells.
3. EBER induces insulin-like growth factor 1 (IGF-1) and promotes autocrine growth of EBV-positive gastric carcinoma.
4. EBV BARF1 gene is known to be a lytic gene and to induce malignant transformation of rodent fibroblasts. We demonstrated that BARF1 is expressed in most EBV-positive gastric carcinoma tissues as a latent gene.
5. It is known that EBV latent membrane protein 2A (LMP2A) gene is expressed in the majority of EBV-positive gastric carcinoma tissues. We demonstrated that LMP2A confers resistance to anoikis in epithelial cells via activation of ERK.
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