Molecular mechanisms of development of gastric carcinoma by Epstein-Barr virus

EB病毒引起胃癌的分子机制

• 批准号: 12213001
• 负责人: TAKADA Kenzo
• 金额: $ 29.57万
• 依托单位: Hokkaido University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research on Priority Areas
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12213001/
• 关键词: 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

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.

本项目旨在阐明EBV诱导胃癌的分子机制，得到以下研究结果：1. EBV诱导胃癌的分子机制。EBV感染上皮细胞有两种不同的途径，gp350依赖性途径和gp350非依赖性途径，gp25可在部分上皮细胞感染中发挥作用。ebv编码的小RNA （EBER）结合干扰素诱导蛋白激酶PKR，抑制其磷酸化，并赋予抵抗fas介导的上皮细胞凋亡的能力。3 . EBER诱导胰岛素样生长因子1 (IGF-1)，促进ebv阳性胃癌的自分泌生长。EBV BARF1基因是一种裂解性基因，可诱导啮齿动物成纤维细胞恶性转化。我们证实BARF1作为潜伏基因在大多数ebv阳性胃癌组织中表达。已知EBV潜伏膜蛋白2A （LMP2A）基因在大多数EBV阳性胃癌组织中表达。我们证明LMP2A通过激活ERK在上皮细胞中赋予对anoikis的抗性。

项目成果

Epstein-Barr virus (EBV)-encoded BARF1 gene is expressed in nasopharyngeal carcinoma and EBV-associated gastric carcinoma tissues in the absence of lytic gene expression: implication of a new EBV latency type.

EB 病毒 (EBV) 编码的 BARF1 基因在鼻咽癌和 EBV 相关胃癌组织中表达，但没有裂解基因表达：新的 EBV 潜伏类型的暗示。

• 发表时间: 2005
• 期刊: J. Med. Virol. 76
• 作者: Seto;E.;Yang;L.;Middeldorp;J.;Sheen;J.S.;Chen;J.Y.;Eizuru;Y.;Takada;K.
• 通讯作者: K.

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