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Blood, 15 April 2006, Vol. 107, No. 8, pp. 3295-3302. Prepublished online as a Blood First Edition Paper on December 27, 2005; DOI 10.1182/blood-2005-07-2730. This Article Full Text (PDF) All Versions of this Article: 2005-07-2730v1 107/8/3295    most recent Alert me when this article is cited Alert me if a correction is posted 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 Keller, S. A Articles by Cesarman, E. Search for Related Content PubMed PubMed Citation Articles by Keller, S. A Articles by Cesarman, E. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 11, 2005 Accepted November 24, 2005 NF-B is essential for progression of KSHV- and EBV-infected lymphomas in vivo Shannon A Keller, Denise Hernandez-Hopkins, Jelena Vider, Vladimir Ponomarev, Elizabeth Hyjek, Elaine J Schattner, and Ethel Cesarman* Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, New York, NY, USA Department of Molecular Pharmacology and Chemistry, Memorial Sloan-Kettering Cancer Center, New York, NY, USA Department of Medicine, Division of Hematology and Oncology, Weill Medical College of Cornell University, New York, NY, USA * Corresponding author; email: ecesarm{at}med.cornell.edu. Activated NF-B is a critical mechanism by which lymphoma cells infected by Epstein-Barr virus (EBV/HHV-4) and Kaposi's sarcoma herpesvirus (KSHV/HHV-8) are protected from apoptotic stress. Selective pharmacological inhibition of constitutive NF-B activity induces apoptosis in both KSHV and EBV infected lymphoma cells. In both tumor types, pharmacologic inhibition of NF-B in vitro induced identical mitochondrially-mediated apoptotic cascades. Assessment of gene regulation by microarray analysis revealed that inhibition of NF-B in tumor cells results in down-regulation of a distinct group of pro-survival genes including cIAP-1, cIAP-2, cFLIP and IL-6. Using EBV and KSHV-associated lymphomas in a murine system, we demonstrate that Bay 11-7082, a selective pharmacological inhibitor of NF-B, prevents or delays tumor growth and prolongs disease-free survival. Inhibition of NF-B activity and tumor growth responses were further documented using a traceable reporter KSHV-positive cell line and in vivo imaging. These findings indicate that specific NF-B regulated survival factors work cooperatively to protect KSHV and EBV infected lymphoma cells from apoptotic stimuli, such that they promote establishment and progression of both KSHV and EBV-associated lymphomas in mice. They also support the use of selective NF-B inhibitors in the treatment of herpesvirus-associated lymphomas. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Y. Etzion, A. Hackett, B. M. Proctor, J. Ren, B. Nolan, T. Ellenberger, and A. J. Muslin An Unbiased Chemical Biology Screen Identifies Agents That Modulate Uptake of Oxidized LDL by Macrophages Circ. Res., July 17, 2009; 105(2): 148 - 157. [Abstract] [Full Text] [PDF] L. T. Krug, C. M. Collins, L. M. Gargano, and S. H. Speck NF-{kappa}B p50 Plays Distinct Roles in the Establishment and Control of Murine Gammaherpesvirus 68 Latency J. Virol., May 15, 2009; 83(10): 4732 - 4748. 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