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Blood, 1 December 2005, Vol. 106, No. 12, pp. 3940-3947. Prepublished online as a Blood First Edition Paper on August 11, 2005; DOI 10.1182/blood-2005-03-1167. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-03-1167v1 106/12/3940    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 Pham, L. V. Articles by Ford, R. J. Search for Related Content PubMed PubMed Citation Articles by Pham, L. V. Articles by Ford, R. J. Related Collections Neoplasia Apoptosis Oncogenes and Tumor Suppressors Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Constitutive NF-B and NFAT activation in aggressive B-cell lymphomas synergistically activates the CD154 gene and maintains lymphoma cell survival Lan V. Pham, Archito T. Tamayo, Linda C. Yoshimura, Yen-Chiu Lin-Lee, and Richard J. Ford From the Department of Hematopathology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, and the Program in Cancer Biology, The University of Texas Graduate School of Biomedical Sciences at Houston, TX. Abnormalities in B-lymphocyte CD40 ligand (CD154) expression have been described for a number of immunologic diseases, including B-cell lymphomas. Although functional analysis of the CD154 gene and protein has been extensive, little is known about the mechanisms controlling CD154 expression in activated T cells, and even less is known for normal and malignant B cells. In this study we describe the transcriptional mechanism controlling CD154 expression in large B-cell lymphoma (LBCL). We show that the nuclear factor of activated T cells (NFAT) transcription factor is also constitutively activated in LBCL. We demonstrate that the constitutively active NFATc1 and c-rel members of the NFAT and nuclear factor–B (NF-B) families of transcription factors, respectively, directly interact with each other, bind to the CD154 promoter, and synergistically activate CD154 gene transcription. Down-regulation of NFATc1 or c-rel with small interfering RNA (siRNA) or chemical inhibitors inhibits CD154 gene transcription and lymphoma cell growth. These findings suggest that targeting NF-B and NFAT, by inhibiting the expression of these transcription factors, or interdicting their interaction may provide a therapeutic rationale for patients with non-Hodgkin lymphoma of B-cell origin, and possibly other disorders that display dysregulated CD154 expression. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. Fu, Y.-C. Lin-Lee, L. V. Pham, A. T. Tamayo, L. C. Yoshimura, and R. J. Ford BAFF-R promotes cell proliferation and survival through interaction with IKK{beta} and NF-{kappa}B/c-Rel in the nucleus of normal and neoplastic B-lymphoid cells Blood, May 7, 2009; 113(19): 4627 - 4636. [Abstract] [Full Text] [PDF] B. K. Robbs, A. L. S. Cruz, M. B. F. Werneck, G. P. Mognol, and J. P. B. Viola Dual Roles for NFAT Transcription Factor Genes as Oncogenes and Tumor Suppressors Mol. Cell. Biol., December 1, 2008; 28(23): 7168 - 7181. [Abstract] [Full Text] [PDF] A. Akimzhanov, L. Krenacs, T. Schlegel, S. Klein-Hessling, E. Bagdi, E. Stelkovics, E. Kondo, S. Chuvpilo, P. Wilke, A. Avots, et al. Epigenetic Changes and Suppression of the Nuclear Factor of Activated T Cell 1 (NFATC1) Promoter in Human Lymphomas with Defects in Immunoreceptor Signaling Am. J. Pathol., January 1, 2008; 172(1): 215 - 224. [Abstract] [Full Text] [PDF] H.-J. Zhou, L. V. Pham, A. T. Tamayo, Y.-C. Lin-Lee, L. Fu, L. C. Yoshimura, and R. J. Ford Nuclear CD40 interacts with c-Rel and enhances proliferation in aggressive B-cell lymphoma Blood, September 15, 2007; 110(6): 2121 - 2127. [Abstract] [Full Text] [PDF] R. Stewart, W. Wei, A. Challa, R. J. Armitage, J. R. Arrand, M. Rowe, L. S. Young, A. Eliopoulos, and J. Gordon CD154 Tone Sets the Signaling Pathways and Transcriptome Generated in Model CD40-Pluricompetent L3055 Burkitt's Lymphoma Cells J. Immunol., September 1, 2007; 179(5): 2705 - 2712. [Abstract] [Full Text] [PDF] R. Loewe, T. Valero, S. Kremling, B. Pratscher, R. Kunstfeld, H. Pehamberger, and P. Petzelbauer Dimethylfumarate Impairs Melanoma Growth and Metastasis Cancer Res., December 15, 2006; 66(24): 11888 - 11896. [Abstract] [Full Text] [PDF]

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