Amplicons on chromosome 3 contain oncogenes induced by recurrent exposure to 12-O-tetradecanoylphorbol-13-acetate and sodium n-butyrate and Epstein-Barr virus reactivation in a nasopharyngeal carcinoma cell line.
Nasopharyngeal carcinoma (NPC) is closely associated with Epstein-Barr virus (EBV) infection and exposure to environmental carcinogens. In this study, an inducible Epstein-Barr virus (EBV) reactivation NPC cell line, NA, was used to investigate the impact of recurrent 12-O-tetradecanoylphorbol-13-acetate-sodium n-butyrate (TPA/SB) treatment and EBV reactivation on chromosomal abnormalities utilizing array-based comparative genomic hybridization (CGH). It was observed that most copy-number aberrations (CNA) were progressively nonrandomly clustered on chromosomes 3, 8, and 9, as the frequency of TPA/SB treatment and EBV reactivation increased. All of the prominent amplicons detected (including 3p14.1, 3p13, 3p12.3, 3p12.2, 3q26.2, 3q26.31, and 3q26.32) were located on chromosome 3, with multiple oncogenes assigned to these sites. The amplification patterns of 3p12.3 and 3q26.2 were validated using fluorescence in situ hybridization (FISH) analysis. Subsequent quantitative real-time polymerase chain reaction detected increasing expression of ROBO1 and SKIL oncogenes in NA cells harboring higher frequency of TPA/SB treatment and EBV reactivation, consistent with copy-number amplification of these loci. These findings demonstrate that a high incidence of TPA/SB induced-EBV reactivation has a profound influence on the carcinogenesis of NPC through altered DNA copy number.
Lee
Chia-Huei
CH
National Institute of Cancer Research, National Health Research Institutes, R2, R1211, Keyan Road, Zhunan Town, Miaoli County 350, Taiwan.
Fang
Chih-Yeu
CY
Sheu
Jim Jinn-Chyuan
JJ
Chang
Yao
Y
Takada
Kenzo
K
Chen
Jen-Yang
JY
D002087:Butyrates / Q000494:pharmacology*; D002273:Carcinogens / Q000494:pharmacology; D002277:Carcinoma / Q000473:pathology / Q000821:virology; D045744:Cell Line, Tumor; D002893:Chromosomes, Human, Pair 3; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000502:physiology; D006801:Humans; D009303:Nasopharyngeal Neoplasms / Q000473:pathology / Q000821:virology*; D009857:Oncogenes; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014775:Virus Activation / Q000187:drug effects
D002087:Butyrates; D002273:Carcinogens; D013755:Tetradecanoylphorbol Acetate