title: Epstein-Barr virus infection alters cellular signal cascades in human nasopharyngeal epithelial cells.
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.
authors.affiliation: Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.
authors.forename: Angela Kwok Fung
authors.initials: AK
authors.lastname: Lo
authors.forename: Kwok Wai
authors.initials: KW
authors.lastname: Lo
authors.forename: Sai Wah
authors.initials: SW
authors.lastname: Tsao
authors.forename: Hing Lok
authors.initials: HL
authors.lastname: Wong
authors.forename: Jan Wai Ying
authors.initials: JW
authors.lastname: Hui
authors.forename: Ka Fai
authors.initials: KF
authors.lastname: To
authors.forename: Diane S
authors.initials: DS
authors.lastname: Hayward
authors.forename: Yiu Loon
authors.initials: YL
authors.lastname: Chui
authors.forename: Yu Lung
authors.initials: YL
authors.lastname: Lau
authors.forename: Kenzo
authors.initials: K
authors.lastname: Takada
authors.forename: Dolly P
authors.initials: DP
authors.lastname: Huang
mesh_terms: D002277:Carcinoma / Q000276:immunology / Q000473:pathology* / Q000821:virology; D002460:Cell Line / Q000502:physiology / Q000821:virology; D045744:Cell Line, Tumor; D002472:Cell Transformation, Viral; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004847:Epithelial Cells / Q000502:physiology / Q000821:virology*; D020031:Epstein-Barr Virus Infections / Q000503:physiopathology*; D015972:Gene Expression Regulation, Neoplastic; D015967:Gene Expression Regulation, Viral; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D007249:Inflammation; D020935:MAP Kinase Signaling System; D016328:NF-kappa B / Q000502:physiology; D009303:Nasopharyngeal Neoplasms / Q000276:immunology / Q000473:pathology* / Q000821:virology; D009305:Nasopharynx / Q000166:cytology*; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000502:physiology; D015398:Signal Transduction; D017735:Virus Latency; D019892:eIF-2 Kinase / Q000502:physiology
chemical_list: D016207:Cytokines; D016328:NF-kappa B; D009363:Neoplasm Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D019892:eIF-2 Kinase