O'Neil, J. D., Owen, T. J., Wood, V. H. J., Date, K. L., Valentine, R., Chukwuma, M. B., Arrand, J. R. (John R.), Dawson, C. W. and Young, Lawrence S. (2008) Epstein-Barr virus-encoded EBNA1 modulates the AP-1 transcription factor pathway in nasopharyngeal carcinoma cells and enhances angiogenesis in vitro. Journal of General Virology, Vol.89 (No.11). pp. 2833-2842. doi:10.1099/vir.0.2008/003392-0 ISSN 0022-1317.

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Abstract

The Epstein–Barr virus (EBV)-encoded EBNA1 protein is expressed in all virus-associated tumours, including nasopharyngeal carcinoma (NPC), where it plays an essential role in EBV genome maintenance, replication and transcription. Previous studies suggest that EBNA1 may have additional effects relevant to oncogenesis, including enhancement of cell survival, raising the possibility that EBNA1 may influence cellular gene expression. We have recently demonstrated by gene expression microarray profiling in an NPC cell model that EBNA1 influences the expression of a range of cellular genes, including those involved in transcription, translation and cell signalling. Here, we report for the first time that EBNA1 enhances activity of the AP-1 transcription factor in NPC cells and demonstrate that this is achieved by EBNA1 binding to the promoters of c-Jun and ATF2, enhancing their expression. In addition, we demonstrate elevated expression of the AP-1 targets interleukin 8, vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1α in response to EBNA1 expression, which enhances microtubule formation in an in vitro angiogenesis assay. Furthermore, we confirm elevation of VEGF and the phosphorylated isoforms of c-Jun and ATF2 in NPC biopsies. These findings implicate EBNA1 in the angiogenic process and suggest that this viral protein might directly contribute to the development and aggressively metastatic nature of NPC.

Item Type:	Journal Article
Divisions:	Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School
Journal or Publication Title:	Journal of General Virology
Publisher:	Society for General Microbiology
ISSN:	0022-1317
Official Date:	November 2008
Dates:	Date Event November 2008 Published
Volume:	Vol.89
Number:	No.11
Page Range:	pp. 2833-2842
DOI:	10.1099/vir.0.2008/003392-0
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Restricted or Subscription Access

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