title: Epstein-Barr virus BALF3 mediates genomic instability and progressive malignancy in nasopharyngeal carcinoma.
abstract: Nasopharyngeal carcinoma (NPC) is a head and neck cancer prevalent throughout Southern China and Southeast Asia. Patient death following relapse after primary treatment remains all too common but the cause of NPC relapse is unclear. Clinical and epidemiological studies have revealed the high correlation among NPC development, Epstein-Barr virus (EBV) reactivation and host genomic instability. Previously, recurrent EBV reactivation was shown to cause massive genetic alterations and enhancement of tumor progression in NPC cells and these may be required for NPC relapse. Here, EBV BALF3 has the ability to induce micronuclei and DNA strand breaks. After recurrent expression of BALF3 in NPC cells, genomic copy number aberrations, determined by array-based comparative genomic hybridization, had accumulated to a significant extent and tumorigenic features, such as cell migration, cell invasion and spheroid formation, increased with the rounds of induction. In parallel experiments, cells after highly recurrent induction developed into larger tumor nodules than control cells when inoculated into NOD/SCID mice. Furthermore, RNA microarrays showed that differential expression of multiple cancer capability-related genes and oncogenes increased with recurrent BALF3 expression and these changes correlated with genetic aberrations. Therefore, EBV BALF3 is a potential factor that mediates the impact of EBV on NPC relapse.
authors.affiliation: Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan. National Institute of Cancer Research, National Health Research Institutes, Miaoli, Taiwan.
authors.forename: Shih-Hsin
authors.initials: SH
authors.lastname: Chiu
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Miaoli, Taiwan.
authors.forename: Chung-Chun
authors.initials: CC
authors.lastname: Wu
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Miaoli, Taiwan.
authors.forename: Chih-Yeu
authors.initials: CY
authors.lastname: Fang
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, Taiwan.
authors.forename: Shu-Ling
authors.initials: SL
authors.lastname: Yu
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Miaoli, Taiwan.
authors.forename: Hui-Yu
authors.initials: HY
authors.lastname: Hsu
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, Taiwan.
authors.forename: Yen-Hung
authors.initials: YH
authors.lastname: Chow
authors.affiliation: Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan. National Institute of Cancer Research, National Health Research Institutes, Miaoli, Taiwan.
authors.forename: Jen-Yang
authors.initials: JY
authors.lastname: Chen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002277:Carcinoma; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002472:Cell Transformation, Viral; D056915:DNA Copy Number Variations; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004318:Doxycycline / Q000494:pharmacology; D004706:Endodeoxyribonucleases / Q000235:genetics / Q000378:metabolism*; D020031:Epstein-Barr Virus Infections / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D055106:Genome-Wide Association Study; D042822:Genomic Instability; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D054884:Host-Pathogen Interactions; D006801:Humans; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D048629:Micronuclei, Chromosome-Defective; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D034622:RNA Interference; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D014764:Viral Proteins; C000598748:BALF3 protein, human herpesvirus 4; D004706:Endodeoxyribonucleases; D004318:Doxycycline