| Project/Area Number |
16591354
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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 | Teikyo University |
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Principal Investigator |
FUKUSHIMA Ryoji Teikyo University, School of Medicine, Department of Surgery, Professor, 医学部, 教授 (50228897)
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| Co-Investigator(Kenkyū-buntansha) |
OKINAGA Kota Teikyo University, School of Medicine, Department of Surgery, Professor, 医学部, 教授 (00101098)
TAJIMA Masako Teikyo University, School of Medicine, Department of Surgery, Assistant, 医学部, 助手 (20211360)
川口 寧 名古屋大学, 大学院・医学研究科, 助教授 (60292984)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2004: ¥2,900,000 (Direct Cost: ¥2,900,000)
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| Keywords | Epstein-Barr virus / carcinogenisis / EBER / LMP-1 / Balb / c mouse / EBV infection / 胃癌 / EBV / マウス / EBウイルス / 消化器感染 / マウス感染 / EBV-NA / EBV-LHP-1 / EBV-EBER / GTC-4-EBV |
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| Research Abstract |
Epstein-Barr virus (EBV) has been implicated in the pathogenesis of some type of gastric adenocarcinoma. We established an epithelial cell line (GTC-4) derived form human gastric cancer tissue. The cell line have a capacity of producing EBV. We further cloned EBV producing cell line GTC-5 from GTC-4 cells and found that digestive tract of Balb/c mice can be infected by EBV produced by GTC-5 (GTC-5-EBV) and finally infected mice developed adenocarcinoma of the digestive tract.
Balb/c mice were gavaged with 0.2ml of 50% ethanol to produce gastric mucosal injury and than GTC-5-EBV were gavaged. Histoimmunostaining showed that EBV nuclear antigen NA-2 were positive in the gastric mucosa 24 hours after the gavage of EBV and disappeared in 21 days. NA-1 and LMP-1 (latent membrane protein 1) were also present in gastric mucosa 5 days after the gavage and disappeared 6 months later. EBER (EBV-encoded small RNA) were identified in the gastric mucosa by in situ hybridization 24 hours after the gavage and it lasted for 9 months. EBER positive adenocarcinoma were developed in the stomach 9 months after the gavage of EBV.
In the next experiment, Balb/c nude mice (6-7W and 10 month, n=10 each) were used to evaluate the carcinogenesis of GTC-5-EBV. GTC-5-EBV was injected weekly for 8 times. After 4 months, adenocarcinoma were found in the rectum of 100 % of elderly mice. In contrast, no cancer was found in the young mice during the observation period of 6 months.
Our model of EBV associated carcinogenisis of digestive tract seems useful in studying the etiology and treatment of EBV associated disorders.
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