1. Epstein-Barr virus infection alters cellular signal cascades in human nasopharyngeal epithelial cells.
- Author
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Lo AK, Lo KW, Tsao SW, Wong HL, Hui JW, To KF, Hayward DS, Chui YL, Lau YL, Takada K, and Huang DP
- Subjects
- Carcinoma immunology, Carcinoma virology, Cell Line physiology, Cell Line virology, Cell Line, Tumor, Cytokines biosynthesis, Cytokines genetics, Epithelial Cells physiology, Gene Expression Regulation, Neoplastic, Gene Expression Regulation, Viral, Humans, Inflammation, MAP Kinase Signaling System, NF-kappa B physiology, Nasopharyngeal Neoplasms immunology, Nasopharyngeal Neoplasms virology, Neoplasm Proteins biosynthesis, Neoplasm Proteins genetics, Phosphorylation, Protein Processing, Post-Translational, Reverse Transcriptase Polymerase Chain Reaction, STAT3 Transcription Factor physiology, Virus Latency, eIF-2 Kinase physiology, Carcinoma pathology, Cell Transformation, Viral, Epithelial Cells virology, Epstein-Barr Virus Infections physiopathology, Herpesvirus 4, Human physiology, Nasopharyngeal Neoplasms pathology, Nasopharynx cytology, Signal Transduction
- Abstract
Epstein-Barr virus (EBV) latent infection is a critical event in nasopharyngeal carcinoma (NPC) tumorigenesis. EBV-encoded genes have been shown to be involved in immune evasion and in the regulation of various cellular signaling cascades. To elucidate the roles of EBV in NPC development, stable infection of EBV in nasopharyngeal epithelial cell lines was established. Similar to primary tumors of NPC, these infected cells exhibited a type II EBV latency expression pattern. In this study, multiple cellular signaling pathways in EBV-infected cells were investigated. We first demonstrated that in vitro EBV infection resulted in the activation of STAT3 and NFkappaB signal cascades in nasopharyngeal epithelial cells. Increased expression of their downstream targets (c-Myc, Bcl-xL, IL-6, LIF, SOCS-1, SOCS-3, VEGF, and COX-2) was also observed. Moreover, EBV latent infection induced the suppression of p38-MAPK activities, but did not activate PKR cascade. Our findings suggest that EBV latent infection is able to manipulate multiple cellular signal cascades to protect infected cells from immunologic attack and to facilitate cancer development.
- Published
- 2006
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