title: Synergism of BARF1 with Ras induces malignant transformation in primary primate epithelial cells and human nasopharyngeal epithelial cells.
abstract: Although it is well known that nasopharyngeal carcinoma (NPC) is closely related with Epstein-Barr virus (EBV), few data are available about which and how EBV-expressed gene is involved in the carcinogenesis of human nasopharyngeal epithelial cells. EBV-encoded BARF1 (BamH I-A right frame 1) gene has been shown to be oncogenic and capable of inducing malignant transformation in BALB/c3T3 and NIH3T3 cells as well as in human B-cell lines Louckes and Akata. It remains unclear, however, whether BARF1 can transform primate or human epithelial cells. Here, we have shown that overexpression of H-Ras gene transformed BARF1-immortalized PATAS cells into malignant cell line. Furthermore, we found that cooperation of BARF1 with H-Ras and SV40 T antigens was sufficient to transform nonmalignant human nasopharyngeal epithelial NP69 cells when serially introduced BARF1 and H-Ras into the SV40 T antigens-immortalized NP69 cells. Taken together, these results demonstrated that the cooperation of BARF1 with Ras suffices to transform primary primate epithelial cell PATAS. Similarly, BARF1 together with H-Ras and SV40 T can transform human epithelial cell NP69, thereby indicating that BARF1 could be involved in the NPC pathogenesis in combination with additional genetic changes.
authors.affiliation: Department of Thoracic Oncology, Tianjin Lung Cancer Center, Tianjin Cancer Institute & Hospital, Tianjin Medical University, Tianjin 300060, China. jrc_0717@yahoo.com
authors.forename: Richeng
authors.initials: R
authors.lastname: Jiang
authors.forename: Giulia
authors.initials: G
authors.lastname: Cabras
authors.forename: Wang
authors.initials: W
authors.lastname: Sheng
authors.forename: Yixin
authors.initials: Y
authors.lastname: Zeng
authors.forename: Tadamasa
authors.initials: T
authors.lastname: Ooka
mesh_terms: D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics / Q000378:metabolism; D041702:BALB 3T3 Cells; D015153:Blotting, Western; D002471:Cell Transformation, Neoplastic; D002472:Cell Transformation, Viral; D004357:Drug Synergism; D004848:Epithelium / Q000378:metabolism / Q000473:pathology / Q000821:virology; D020031:Epstein-Barr Virus Infections / Q000235:genetics / Q000378:metabolism / Q000821:virology; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D004854:Herpesvirus 4, Human / Q000502:physiology; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000473:pathology / Q000821:virology; D051379:Mice; D008819:Mice, Nude; D041681:NIH 3T3 Cells; D009303:Nasopharyngeal Neoplasms / Q000235:genetics / Q000473:pathology* / Q000821:virology; D011323:Primates / Q000235:genetics / Q000378:metabolism / Q000821:virology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019098:Telomerase / Q000378:metabolism; D014162:Transfection; D014764:Viral Proteins / Q000502:physiology*; D018631:ras Proteins / Q000502:physiology*
chemical_list: D000952:Antigens, Polyomavirus Transforming; C086495:BARF1 protein, Human herpesvirus 4; D012333:RNA, Messenger; D014764:Viral Proteins; D019098:Telomerase; D018631:ras Proteins