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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 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 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 Keller, S. A. Articles by Cesarman, E. Search for Related Content PubMed PubMed Citation Articles by Keller, S. A. Articles by Cesarman, E. Related Collections Signal Transduction Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA NF-B is essential for the 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 From the Department of Pathology and Laboratory Medicine and the Department of Medicine, Division of Hematology and Oncology, Weill Medical College of Cornell University, New York, NY; and the Department of Molecular Pharmacology and Chemistry, Memorial Sloan-Kettering Cancer Center, New York, NY. Activated NF-B is a critical mechanism by which lymphoma cells infected by Epstein-Barr virus (EBV/HHV-4) and Kaposi sarcoma herpesvirus (KSHV/HHV-8) are protected from apoptotic stress. Selective pharmacologic inhibition of constitutive NF-B activity induces apoptosis in KSHV- and EBV-infected lymphoma cells. In both tumor types, pharmacologic inhibition of NF-B in vitro induced identical mitochondrially mediated apoptosis cascades. Assessment of gene regulation by microarray analysis revealed that the inhibition of NF-B in tumor cells results in the down-regulation of a distinct group of prosurvival genes, including cIAP-1, cIAP-2, cFLIP, and IL-6. Using EBV- and KSHV-associated lymphomas in a murine system, we demonstrated that Bay 11-7082, a selective pharmacologic 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 apoptosis such that they promote the establishment and progression of 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: I. Guasparri, D. Bubman, and E. Cesarman EBV LMP2A affects LMP1-mediated NF-{kappa}B signaling and survival of lymphoma cells by regulating TRAF2 expression Blood, April 1, 2008; 111(7): 3813 - 3820. [Abstract] [Full Text] [PDF] M-Q Du, C M Bacon, and P G Isaacson Kaposi sarcoma-associated herpesvirus/human herpesvirus 8 and lymphoproliferative disorders J. Clin. Pathol., December 1, 2007; 60(12): 1350 - 1357. [Abstract] [Full Text] [PDF] A. Orbach, J. Rachmilewitz, M. Parnas, J.-H. Huang, M. L. Tykocinski, and M. Dranitzki-Elhalel CTLA-4 {middle dot} FasL Induces Early Apoptosis of Activated T Cells by Interfering with Anti-Apoptotic Signals J. Immunol., December 1, 2007; 179(11): 7287 - 7294. [Abstract] [Full Text] [PDF] H. Zhang, L. Zhi, S. M. 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Listeria monocytogenes Promotes Tumor Growth via Tumor Cell Toll-Like Receptor 2 Signaling Cancer Res., May 1, 2007; 67(9): 4346 - 4352. [Abstract] [Full Text] [PDF] S. Sadagopan, N. Sharma-Walia, M. V. Veettil, H. Raghu, R. Sivakumar, V. Bottero, and B. Chandran Kaposi's Sarcoma-Associated Herpesvirus Induces Sustained NF-{kappa}B Activation during De Novo Infection of Primary Human Dermal Microvascular Endothelial Cells That Is Essential for Viral Gene Expression J. Virol., April 15, 2007; 81(8): 3949 - 3968. [Abstract] [Full Text] [PDF] H. Zhang, L. Zhi, S. Moochhala, P. K. Moore, and M. Bhatia Hydrogen sulfide acts as an inflammatory mediator in cecal ligation and puncture-induced sepsis in mice by upregulating the production of cytokines and chemokines via NF-{kappa}B Am J Physiol Lung Cell Mol Physiol, April 1, 2007; 292(4): L960 - L971. [Abstract] [Full Text] [PDF] S. Wang, S. Wang, H. Maeng, D. P. Young, O. Prakash, L. E. Fayad, A. Younes, and F. 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