Nuclear Factor-Y and Epstein Barr Virus in Nasopharyngeal Cancer

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Bibliographische Detailangaben
Zeitschriftentitel:	Clinical Cancer Research
Personen und Körperschaften:	Chia, Marie C., Leung, Abby, Krushel, Tiffany, Alajez, Nehad M., Lo, Kwok W., Busson, Pierre, Klamut, Henry J., Bastianutto, Carlo, Liu, Fei-Fei
In:	Clinical Cancer Research, 14, 2008, 4, S. 984-994
Format:	E-Article
Sprache:	Englisch
veröffentlicht:	American Association for Cancer Research (AACR)
Schlagwörter:	Cancer Research Oncology

Details
Zusammenfassung:	<jats:title>Abstract</jats:title> <jats:p>Purpose: The Epstein Barr virus (EBV) is intimately associated with nasopharyngeal cancer (NPC) in a latent state expressing a limited number of genes. The process of switching from latency to replication is not well understood, particularly in response to DNA stress; hence, the focus of this study is on an EBV-positive NPC model.</jats:p> <jats:p>Experimental Design: C666-1 cells were exposed to radiation (2-15 Gy) or cisplatin (0.1-50 μg/mL) assayed subsequently for relative EBV copy number (BamHI) and lytic gene expression (BRLF1 and BZLF1) using quantitative real-time PCR. Chromatin immunoprecipitation was conducted to assess the interaction of the transcription factor nuclear factor-Y (NF-Y) with promoter sequences.</jats:p> <jats:p>Results: Radiation-induced and cisplatin-induced BamHI expression, along with increased levels of BRLF1 and BZLF1 in a dose-dependent and time-dependent manner, associated with the immediate nuclear transactivation of the transcription factor NF-Y and its own increased transcription of NF-Y subunits 8 h posttreatment. In silico analysis revealed three putative NF-Y consensus-binding sequences in the promoter region of BRLF1, which all interacted with NF-Y in response to radiation and cisplatin, confirmed using chromatin immunoprecipitation. Introduction of dominant-negative NF-YA reduced BRLF1 expression after radiation and cisplatin by 2.8-fold; in turn, overexpression of NF-YA resulted in a 2-fold increase in both BRLF1 and BZLF1 expression.</jats:p> <jats:p>Conclusions: These results show that NF-Y is an important mediator of EBV stress response in switching from a latent to lytic state. This novel insight could provide a potential therapeutic strategy to enhance NPC response to radiation and cisplatin.</jats:p>
Umfang:	984-994
ISSN:	1557-3265 1078-0432
DOI:	10.1158/1078-0432.ccr-07-0828