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Blood, 1 January 2008, Vol. 111, No. 1, pp. 292-301. Prepublished online as a Blood First Edition Paper on August 24, 2007; DOI 10.1182/blood-2006-11-059881. This Article Full Text Full Text (PDF) Supplemental Tables and Figures All Versions of this Article: blood-2006-11-059881v1 111/1/292    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Flavell, J. R. Articles by Murray, P. G. Search for Related Content PubMed PubMed Citation Articles by Flavell, J. R. Articles by Murray, P. G. Related Collections Gene Expression Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Down-regulation of the TGF-beta target gene, PTPRK, by the Epstein-Barr virus–encoded EBNA1 contributes to the growth and survival of Hodgkin lymphoma cells Joanne R. Flavell1, Karl R. N. Baumforth1, Victoria H. J. Wood1, Gillian L. Davies1, Wenbin Wei1, Gary M. Reynolds2, Susan Morgan1, Andrew Boyce1, Gemma L. Kelly1, Lawrence S. Young1, and Paul G. Murray1 1 Cancer Research UK Institute for Cancer Studies and 2 Liver Research Laboratories, Medical School, University of Birmingham, Birmingham, United Kingdom The Epstein-Barr virus (EBV) contributes to the growth and survival of Hodgkin lymphoma (HL) cells. Here we report that down-regulation of the transforming growth factor-beta (TGF-beta) target gene, protein tyrosine phosphatase receptor kappa (PTPRK), followed EBV infection of HL cells and was also more frequently observed in the Hodgkin and Reed-Sternberg (HRS) cells of EBV-positive compared with EBV-negative primary HL. The viability and proliferation of EBV-positive HL cells was decreased by overexpression of PTPRK, but increased following the knockdown of PTPRK expression in EBV-negative HL cells, demonstrating that PTPRK is a functional tumor suppressor in HL. EBV suppressed the TGF-beta–mediated activation of PTPRK expression, suggesting disruption of TGF-beta signaling upstream of PTPRK. This was confirmed when we showed that the Epstein-Barr nuclear antigen-1 (EBNA1) decreased Smad2 protein levels and that this was responsible for PTPRK down-regulation. EBNA1 decreased the half-life of Smad2 but did not interact with Smad2. By down-regulating Smad2 protein expression, EBNA1 apparently disables TGF-beta signaling, which subsequently decreases transcription of the PTPRK tumor suppressor. We speculate that loss of the phosphatase function of PTPRK may activate as-yet-unidentified growth-promoting protein tyrosine kinases, which in turn contribute to the pathogenesis of EBV-positive HL. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. R.N. Baumforth, A. Birgersdotter, G. M. Reynolds, W. Wei, G. Kapatai, J. R. Flavell, E. Kalk, K. Piper, S. Lee, L. Machado, et al. Expression of the Epstein-Barr Virus-Encoded Epstein-Barr Virus Nuclear Antigen 1 in Hodgkin's Lymphoma Cells Mediates Up-Regulation of CCL20 and the Migration of Regulatory T Cells Am. J. Pathol., July 1, 2008; 173(1): 195 - 204. [Abstract] [Full Text] [PDF] M.-S. Kang, V. Soni, R. Bronson, and E. Kieff Epstein-Barr Virus Nuclear Antigen 1 Does Not Cause Lymphoma in C57BL/6J Mice J. Virol., April 15, 2008; 82(8): 4180 - 4183. [Abstract] [Full Text] [PDF]

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