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Nuclear factor-Y and Epstein Barr virus in nasopharyngeal cancer.
Clin Cancer Res. 2008 Feb 15; 14(4):984-94.CC

Abstract

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.

EXPERIMENTAL DESIGN

C666-1 cells were exposed to radiation (2-15 Gy) or cisplatin (0.1-50 microg/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.

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.

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.

Authors+Show Affiliations

Department of Medical Biophysics, University of Toronto, Toronto, Canada.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18281530

Citation

Chia, Marie C., et al. "Nuclear factor-Y and Epstein Barr Virus in Nasopharyngeal Cancer." Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, vol. 14, no. 4, 2008, pp. 984-94.
Chia MC, Leung A, Krushel T, et al. Nuclear factor-Y and Epstein Barr virus in nasopharyngeal cancer. Clin Cancer Res. 2008;14(4):984-94.
Chia, M. C., Leung, A., Krushel, T., Alajez, N. M., Lo, K. W., Busson, P., Klamut, H. J., Bastianutto, C., & Liu, F. F. (2008). Nuclear factor-Y and Epstein Barr virus in nasopharyngeal cancer. Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, 14(4), 984-94. https://doi.org/10.1158/1078-0432.CCR-07-0828
Chia MC, et al. Nuclear factor-Y and Epstein Barr Virus in Nasopharyngeal Cancer. Clin Cancer Res. 2008 Feb 15;14(4):984-94. PubMed PMID: 18281530.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Nuclear factor-Y and Epstein Barr virus in nasopharyngeal cancer. AU - Chia,Marie C, AU - Leung,Abby, AU - Krushel,Tiffany, AU - Alajez,Nehad M, AU - Lo,Kwok W, AU - Busson,Pierre, AU - Klamut,Henry J, AU - Bastianutto,Carlo, AU - Liu,Fei-Fei, PY - 2008/2/19/pubmed PY - 2008/6/5/medline PY - 2008/2/19/entrez SP - 984 EP - 94 JF - Clinical cancer research : an official journal of the American Association for Cancer Research JO - Clin Cancer Res VL - 14 IS - 4 N2 - 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. EXPERIMENTAL DESIGN: C666-1 cells were exposed to radiation (2-15 Gy) or cisplatin (0.1-50 microg/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. 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. 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. SN - 1078-0432 UR - https://www.unboundmedicine.com/medline/citation/18281530/Nuclear_factor_Y_and_Epstein_Barr_virus_in_nasopharyngeal_cancer_ L2 - http://clincancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=18281530 DB - PRIME DP - Unbound Medicine ER -