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

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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.