PMID- 18656687 OWN - NLM STAT- MEDLINE DCOM- 20080815 LR - 20131121 IS - 1873-4456 (Electronic) IS - 0165-4608 (Linking) VI - 185 IP - 1 DP - 2008 Aug TI - 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. PG - 1-10 LID - 10.1016/j.cancergencyto.2008.03.014 [doi] AB - 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. FAU - Lee, Chia-Huei AU - Lee CH AD - National Institute of Cancer Research, National Health Research Institutes, R2, R1211, Keyan Road, Zhunan Town, Miaoli County 350, Taiwan. FAU - Fang, Chih-Yeu AU - Fang CY FAU - Sheu, Jim Jinn-Chyuan AU - Sheu JJ FAU - Chang, Yao AU - Chang Y FAU - Takada, Kenzo AU - Takada K FAU - Chen, Jen-Yang AU - Chen JY LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Cancer Genet Cytogenet JT - Cancer genetics and cytogenetics JID - 7909240 RN - 0 (Butyrates) RN - 0 (Carcinogens) RN - NI40JAQ945 (Tetradecanoylphorbol Acetate) SB - IM MH - Butyrates/*pharmacology MH - Carcinogens/pharmacology MH - Carcinoma/pathology/virology MH - Cell Line, Tumor MH - *Chromosomes, Human, Pair 3 MH - Herpesvirus 4, Human/*genetics/physiology MH - Humans MH - Nasopharyngeal Neoplasms/pathology/*virology MH - *Oncogenes MH - Tetradecanoylphorbol Acetate/*pharmacology MH - Virus Activation/drug effects EDAT- 2008/07/29 09:00 MHDA- 2008/08/16 09:00 CRDT- 2008/07/29 09:00 PHST- 2007/11/14 00:00 [received] PHST- 2008/03/24 00:00 [revised] PHST- 2008/03/28 00:00 [accepted] PHST- 2008/07/29 09:00 [pubmed] PHST- 2008/08/16 09:00 [medline] PHST- 2008/07/29 09:00 [entrez] AID - S0165-4608(08)00233-1 [pii] AID - 10.1016/j.cancergencyto.2008.03.014 [doi] PST - ppublish SO - Cancer Genet Cytogenet. 2008 Aug;185(1):1-10. doi: 10.1016/j.cancergencyto.2008.03.014.