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Nuclear Factor-Y and Epstein Barr Virus in Nasopharyngeal Cancer
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| Zeitschriftentitel: | Clinical Cancer Research |
|---|---|
| Personen und Körperschaften: | , , , , , , , , |
| In: | Clinical Cancer Research, 14, 2008, 4, S. 984-994 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Association for Cancer Research (AACR)
|
| Schlagwörter: |
| author_facet |
Chia, Marie C. Leung, Abby Krushel, Tiffany Alajez, Nehad M. Lo, Kwok W. Busson, Pierre Klamut, Henry J. Bastianutto, Carlo Liu, Fei-Fei Chia, Marie C. Leung, Abby Krushel, Tiffany Alajez, Nehad M. Lo, Kwok W. Busson, Pierre Klamut, Henry J. Bastianutto, Carlo Liu, Fei-Fei |
|---|---|
| author |
Chia, Marie C. Leung, Abby Krushel, Tiffany Alajez, Nehad M. Lo, Kwok W. Busson, Pierre Klamut, Henry J. Bastianutto, Carlo Liu, Fei-Fei |
| spellingShingle |
Chia, Marie C. Leung, Abby Krushel, Tiffany Alajez, Nehad M. Lo, Kwok W. Busson, Pierre Klamut, Henry J. Bastianutto, Carlo Liu, Fei-Fei Clinical Cancer Research Nuclear Factor-Y and Epstein Barr Virus in Nasopharyngeal Cancer Cancer Research Oncology |
| author_sort |
chia, marie c. |
| spelling |
Chia, Marie C. Leung, Abby Krushel, Tiffany Alajez, Nehad M. Lo, Kwok W. Busson, Pierre Klamut, Henry J. Bastianutto, Carlo Liu, Fei-Fei 1078-0432 1557-3265 American Association for Cancer Research (AACR) Cancer Research Oncology http://dx.doi.org/10.1158/1078-0432.ccr-07-0828 <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> Nuclear Factor-Y and Epstein Barr Virus in Nasopharyngeal Cancer Clinical Cancer Research |
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10.1158/1078-0432.ccr-07-0828 |
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American Association for Cancer Research (AACR), 2008 |
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American Association for Cancer Research (AACR), 2008 |
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1557-3265 1078-0432 |
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1557-3265 1078-0432 |
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Clinical Cancer Research |
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| title |
Nuclear Factor-Y and Epstein Barr Virus in Nasopharyngeal Cancer |
| title_unstemmed |
Nuclear Factor-Y and Epstein Barr Virus in Nasopharyngeal Cancer |
| title_full |
Nuclear Factor-Y and Epstein Barr Virus in Nasopharyngeal Cancer |
| title_fullStr |
Nuclear Factor-Y and Epstein Barr Virus in Nasopharyngeal Cancer |
| title_full_unstemmed |
Nuclear Factor-Y and Epstein Barr Virus in Nasopharyngeal Cancer |
| title_short |
Nuclear Factor-Y and Epstein Barr Virus in Nasopharyngeal Cancer |
| title_sort |
nuclear factor-y and epstein barr virus in nasopharyngeal cancer |
| topic |
Cancer Research Oncology |
| url |
http://dx.doi.org/10.1158/1078-0432.ccr-07-0828 |
| publishDate |
2008 |
| physical |
984-994 |
| description |
<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> |
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| author | Chia, Marie C., Leung, Abby, Krushel, Tiffany, Alajez, Nehad M., Lo, Kwok W., Busson, Pierre, Klamut, Henry J., Bastianutto, Carlo, Liu, Fei-Fei |
| author_facet | Chia, Marie C., Leung, Abby, Krushel, Tiffany, Alajez, Nehad M., Lo, Kwok W., Busson, Pierre, Klamut, Henry J., Bastianutto, Carlo, Liu, Fei-Fei, Chia, Marie C., Leung, Abby, Krushel, Tiffany, Alajez, Nehad M., Lo, Kwok W., Busson, Pierre, Klamut, Henry J., Bastianutto, Carlo, Liu, Fei-Fei |
| author_sort | chia, marie c. |
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| container_start_page | 984 |
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| description | <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> |
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| imprint | American Association for Cancer Research (AACR), 2008 |
| imprint_str_mv | American Association for Cancer Research (AACR), 2008 |
| institution | DE-Gla1, DE-Zi4, DE-15, DE-Pl11, DE-Rs1, DE-105, DE-14, DE-Ch1, DE-L229, DE-D275, DE-Bn3, DE-Brt1, DE-Zwi2, DE-D161 |
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| spelling | Chia, Marie C. Leung, Abby Krushel, Tiffany Alajez, Nehad M. Lo, Kwok W. Busson, Pierre Klamut, Henry J. Bastianutto, Carlo Liu, Fei-Fei 1078-0432 1557-3265 American Association for Cancer Research (AACR) Cancer Research Oncology http://dx.doi.org/10.1158/1078-0432.ccr-07-0828 <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> Nuclear Factor-Y and Epstein Barr Virus in Nasopharyngeal Cancer Clinical Cancer Research |
| spellingShingle | Chia, Marie C., Leung, Abby, Krushel, Tiffany, Alajez, Nehad M., Lo, Kwok W., Busson, Pierre, Klamut, Henry J., Bastianutto, Carlo, Liu, Fei-Fei, Clinical Cancer Research, Nuclear Factor-Y and Epstein Barr Virus in Nasopharyngeal Cancer, Cancer Research, Oncology |
| title | Nuclear Factor-Y and Epstein Barr Virus in Nasopharyngeal Cancer |
| title_full | Nuclear Factor-Y and Epstein Barr Virus in Nasopharyngeal Cancer |
| title_fullStr | Nuclear Factor-Y and Epstein Barr Virus in Nasopharyngeal Cancer |
| title_full_unstemmed | Nuclear Factor-Y and Epstein Barr Virus in Nasopharyngeal Cancer |
| title_short | Nuclear Factor-Y and Epstein Barr Virus in Nasopharyngeal Cancer |
| title_sort | nuclear factor-y and epstein barr virus in nasopharyngeal cancer |
| title_unstemmed | Nuclear Factor-Y and Epstein Barr Virus in Nasopharyngeal Cancer |
| topic | Cancer Research, Oncology |
| url | http://dx.doi.org/10.1158/1078-0432.ccr-07-0828 |