title: Epstein-Barr virus (EBV)-encoded BARF1 gene is expressed in nasopharyngeal carcinoma and EBV-associated gastric carcinoma tissues in the absence of lytic gene expression.
abstract: The BARF1 gene is located in the BamHI-A fragment of the Epstein-Barr virus (EBV) genome, encodes 221 amino acids, and has activity as an oncogene. Several reports have demonstrated that BARF1 is expressed in the tissues of various EBV-associated epithelioid malignancies. However,BARF1 is thought to be a lytic gene, since its expression is induced upon induction of the lytic cycle in Burkitt's lymphoma cell lines. Therefore, the possibility cannot be excluded that BARF1 expression in EBV-associated epithelioid malignancies reflects spontaneous induction of the lytic cycle in carcinoma cells. The present study aimed to clarify whether BARF1 was expressed as a latent gene or a lytic gene in epithelioid malignancies. Quantitative real-time RT-PCR assay revealed that BARF1 was highly expressed in nasopharyngeal carcinoma (NPC) and EBV-positive gastric carcinoma tissues in the absence of expression of lytic genes. On the other hand, BARF1 protein was detectable only in two of seven NPC tissue samples by immunoblot analysis. Analysis of BARF1-transfected CNE1 cells revealed that BARF1 was quickly secreted into culture medium and was hardly detectable in the cell lysate, which would account for why some NPC tissues were negative for BARF1 protein expression even though they were strongly positive forBARF1 expression at the transcriptional level. The present findings indicate that BARF1 is expressed in NPC and EBV-positive gastric carcinoma tissues as a latent gene and suggest that BARF1 plays a role in the pathogenesis of these malignancies.
authors.affiliation: Department of Tumor Virology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Eri
authors.initials: E
authors.lastname: Seto
authors.forename: Lixin
authors.initials: L
authors.lastname: Yang
authors.forename: Jaap
authors.initials: J
authors.lastname: Middeldorp
authors.forename: Tzung-Shiahn
authors.initials: TS
authors.lastname: Sheen
authors.forename: Jen-Yan
authors.initials: JY
authors.lastname: Chen
authors.forename: Masashi
authors.initials: M
authors.lastname: Fukayama
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Eizuru
authors.forename: Tadamasa
authors.initials: T
authors.lastname: Ooka
authors.forename: Kenzo
authors.initials: K
authors.lastname: Takada
mesh_terms: D002277:Carcinoma / Q000378:metabolism* / Q000821:virology; D002460:Cell Line; D005814:Genes, Viral; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) / Q000235:genetics / Q000378:metabolism; D004854:Herpesvirus 4, Human; D006801:Humans; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism* / Q000821:virology; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000821:virology; D014162:Transfection; D014764:Viral Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*
chemical_list: C086495:BARF1 protein, Human herpesvirus 4; D014764:Viral Proteins; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating); D016186:Receptor, Macrophage Colony-Stimulating Factor