| Project/Area Number |
18590664
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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 |
Gastroenterology
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| Research Institution | Hokkaido University |
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Principal Investigator |
IWAKIRI Dai Hokkaido University, Institute for Genetic Medicine, Hokkaido University, Assistant Professor (10307853)
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| Project Period (FY) |
2006 – 2007
|
| Project Status |
Completed (Fiscal Year 2007)
|
| Budget Amount *help |
¥3,920,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥420,000)
Fiscal Year 2007: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2006: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | Epstein-Barr virus / Gastirs cancer / EBER / RIG-I / TLR3 / Innate immunity / IGF-I |
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| Research Abstract |
We have previously reported that EBV infection of gastric epithelial cells leads to induction of insulin-like growth factor (IGF)-1 and IGF-1 promotes growth of EBV-infected cells by an autocrine mechanism. We have also identified that EBV-encoded small RNA (EBER) is the responsible gene for IGF-1 induction.
In this study, we analyzed how EBER induced IGF-1 to clarify the mechanisms of EBV-mediated gastric carcinogenesis. We identified that EBER activates retinoic acid-inducible gene (RIG)-I, which is the cytosolic double stranded RNA (ds RNA) sensor, leading to induction of interferon via activation of IRF3 and NF-κB in Burkitt's lymphoma (BL) cells. Furthermore, we found that EBER-mediated RIG-I activation induces IL-10, which acts as a growth factor for BL cells. These are novel findings suggesting that activation of innate immune signals by EBER contributes to growth promotion of EBV-positive cancer cells.
On the other hand, we identified that EBER is released extracellulary from EBV-positive gastric cancer cells leading to induction of TLR3-mediated signal transduction. Our findings indicate that TLR3-mediated signaling is constitutively activated, therefore may contribute to IGF-1 induction by EBER in EBV -positive gastric cancer cells.
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