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

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。

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.