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Related Collections Neoplasia Apoptosis Gene Expression Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 May 2001, Vol. 97, No. 9, pp. 2798-2807 NEOPLASIA Constitutive NF-B maintains high expression of a characteristic gene network, including CD40, CD86, and a set of antiapoptotic genes in Hodgkin/Reed-Sternberg cells Michael Hinz, Peter Löser, Stephan Mathas, Daniel Krappmann, Bernd Dörken, and Claus Scheidereit From the Max Delbrück Center for Molecular Medicine; HepaVec AG; and Humboldt University of Berlin, Universitätsklinikum Charité, Robert Rössle Klinik; all of Berlin, Germany. Constitutively activated nuclear factor (NF)-B is observed in a variety of neoplastic diseases and is a hallmark of the malignant Hodgkin and Reed-Sternberg cells (H/RS) in Hodgkin lymphoma. Given the distinctive role of constitutive NF-B for H/RS cell viability, NF-B-dependent target genes were searched for by using adenoviral expression of the super-repressor IBN. A surprisingly small but characteristic set of genes, including the cell-cycle regulatory protein cyclin D2, the antiapoptotic proteins Bfl-1/A1, c-IAP2, TRAF1, and Bcl-xL, and the cell surface receptors CD86 and CD40 were identified. Thus, constitutive NF-B activity maintains expression of a network of genes, which are known for frequent, marker-like expression in primary or cultured H/RS cells. Intriguingly, CD40, which is able to activate CD86 or Bcl-xL via NF-B, is itself transcriptionally regulated by NF-B through a promoter proximal binding site. NF-B inhibition resulted in massive spontaneous and p53-independent apoptosis, which could be rescued by ectopic expression of Bcl-xL, underscoring its dominant role in survival of H/RS cells. Hence, NF-B controls a signaling network in H/RS cells, which promotes tumor cell growth and confers resistance to apoptosis. © 2001 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: G. Fan, Y. Fan, N. Gupta, I. Matsuura, F. Liu, X. Z. Zhou, K. P. Lu, and C. Gelinas Peptidyl-Prolyl Isomerase Pin1 Markedly Enhances the Oncogenic Activity of the Rel Proteins in the Nuclear Factor-{kappa}B Family Cancer Res., June 1, 2009; 69(11): 4589 - 4597. [Abstract] [Full Text] [PDF] J. Dutta, G. Fan, and C. Gelinas CAPER{alpha} Is a Novel Rel-TAD-Interacting Factor That Inhibits Lymphocyte Transformation by the Potent Rel/NF-{kappa}B Oncoprotein v-Rel J. Virol., November 1, 2008; 82(21): 10792 - 10802. [Abstract] [Full Text] [PDF] J. H. Mendler, J. Kelly, S. Voci, D. Marquis, L. Rich, R. M. Rossi, S. H. Bernstein, C. T. Jordan, J. Liesveld, R. I. Fisher, et al. 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[Abstract] [Full Text] [PDF] K. J. Savage, S. Monti, J. L. Kutok, G. Cattoretti, D. Neuberg, L. de Leval, P. Kurtin, P. D. Cin, C. Ladd, F. Feuerhake, et al. The molecular signature of mediastinal large B-cell lymphoma differs from that of other diffuse large B-cell lymphomas and shares features with classical Hodgkin lymphoma Blood, December 1, 2003; 102(12): 3871 - 3879. [Abstract] [Full Text] [PDF] S. Mathas, A. Lietz, M. Janz, M. Hinz, F. Jundt, C. Scheidereit, K. Bommert, and B. Dorken Inhibition of NF-{kappa}B essentially contributes to arsenic-induced apoptosis Blood, August 1, 2003; 102(3): 1028 - 1034. [Abstract] [Full Text] [PDF] G Siegler, E Kremmer, R Gonnella, and G Niedobitek Epstein-Barr virus encoded latent membrane protein 1 (LMP1) and TNF receptor associated factors (TRAF): colocalisation of LMP1 and TRAF1 in primary EBV infection and in EBV associated Hodgkin lymphoma Mol. Pathol., June 1, 2003; 56(3): 156 - 161. [Abstract] [Full Text] [PDF] T. F. E. Barth, J. I. Martin-Subero, S. Joos, C. K. Menz, C. Hasel, G. Mechtersheimer, R. M. Parwaresch, P. Lichter, R. Siebert, and P. Moller Gains of 2p involving the REL locus correlate with nuclear c-Rel protein accumulation in neoplastic cells of classical Hodgkin lymphoma Blood, May 1, 2003; 101(9): 3681 - 3686. [Abstract] [Full Text] [PDF] J. F. Garcia, F. I. Camacho, M. Morente, M. Fraga, C. Montalban, T. A. C. Bellas, A. Castano, A. Diez, T. Flores, C. Martin, et al. Hodgkin and Reed-Sternberg cells harbor alterations in the major tumor suppressor pathways and cell-cycle checkpoints: analyses using tissue microarrays Blood, January 15, 2003; 101(2): 681 - 689. [Abstract] [Full Text] [PDF] X. Li, P. E. Massa, A. Hanidu, G. W. Peet, P. Aro, A. Savitt, S. Mische, J. Li, and K. B. Marcu IKKalpha , IKKbeta , and NEMO/IKKgamma Are Each Required for the NF-kappa B-mediated Inflammatory Response Program J. Biol. Chem., November 15, 2002; 277(47): 45129 - 45140. [Abstract] [Full Text] [PDF] G. Munzert, D. Kirchner, H. Stobbe, L. Bergmann, R. M. Schmid, H. Dohner, and H. Heimpel Tumor necrosis factor receptor-associated factor 1 gene overexpression in B-cell chronic lymphocytic leukemia: analysis of NF-kappa B/Rel-regulated inhibitors of apoptosis Blood, November 15, 2002; 100(10): 3749 - 3756. [Abstract] [Full Text] [PDF] M. Hinz, P. Lemke, I. Anagnostopoulos, C. Hacker, D. Krappmann, S. Mathas, B. Dorken, M. Zenke, H. Stein, and C. Scheidereit Nuclear Factor {kappa}B-dependent Gene Expression Profiling of Hodgkin's Disease Tumor Cells, Pathogenetic Significance, and Link to Constitutive Signal Transducer and Activator of Transcription 5a Activity J. Exp. Med., September 2, 2002; 196(5): 605 - 617. [Abstract] [Full Text] [PDF] L Leoncini, S Lazzi, C Bellan, and P Tosi Cell kinetics and cell cycle regulation in lymphomas J. Clin. Pathol., September 1, 2002; 55(9): 648 - 655. [Abstract] [Full Text] [PDF] B. F. Skinnider and T. W. Mak The role of cytokines in classical Hodgkin lymphoma Blood, May 29, 2002; 99(12): 4283 - 4297. [Abstract] [Full Text] [PDF] R. J. Steptoe, J. M. Ritchie, and L. C. Harrison Increased Generation of Dendritic Cells from Myeloid Progenitors in Autoimmune-Prone Nonobese Diabetic Mice J. Immunol., May 15, 2002; 168(10): 5032 - 5041. [Abstract] [Full Text] [PDF] F. Jundt, I. Anagnostopoulos, R. Forster, S. Mathas, H. Stein, and B. Dorken Activated Notch1 signaling promotes tumor cell proliferation and survival in Hodgkin and anaplastic large cell lymphoma Blood, May 1, 2002; 99(9): 3398 - 3403. [Abstract] [Full Text] [PDF] H. Bosshart ;, A. Mukhopadhyay, P. Fiumara, Y. Li, B. G. Darnay, B. Aggarwal, and A. Younes Expression of survival receptors in Hodgkin disease cell lines Blood, May 1, 2002; 99(9): 3484 - 3486. [Full Text] [PDF] U. E. Hopken, H.-D. Foss, D. Meyer, M. Hinz, K. Leder, H. Stein, and M. Lipp Up-regulation of the chemokine receptor CCR7 in classical but not in lymphocyte-predominant Hodgkin disease correlates with distinct dissemination of neoplastic cells in lymphoid organs Blood, February 15, 2002; 99(4): 1109 - 1116. [Abstract] [Full Text] [PDF] J. I. Martin-Subero, S. Gesk, L. Harder, T. Sonoki, P. W. Tucker, B. Schlegelberger, W. Grote, F. J. Novo, M. J. Calasanz, M. L. Hansmann, et al. Recurrent involvement of the REL and BCL11A loci in classical Hodgkin lymphoma Blood, February 15, 2002; 99(4): 1474 - 1477. [Abstract] [Full Text] [PDF] E. Oelmann, H. Herbst, M. Zuhlsdorf, O. Albrecht, A. Nolte, C. Schmitmann, O. Manzke, V. Diehl, H. Stein, and W. E. Berdel Tissue inhibitor of metalloproteinases 1 is an autocrine and paracrine survival factor, with additional immune-regulatory functions, expressed by Hodgkin/Reed-Sternberg cells Blood, January 1, 2002; 99(1): 258 - 267. [Abstract] [Full Text] [PDF] R. E. Davis, K. D. Brown, U. Siebenlist, and L. M. Staudt Constitutive Nuclear Factor {kappa}B Activity Is Required for Survival of Activated B Cell-like Diffuse Large B Cell Lymphoma Cells J. Exp. Med., December 17, 2001; 194(12): 1861 - 1874. [Abstract] [Full Text] [PDF] A. K. Cardozo, H. Heimberg, Y. Heremans, R. Leeman, B. Kutlu, M. Kruhoffer, T. Orntoft, and D. L. Eizirik A Comprehensive Analysis of Cytokine-induced and Nuclear Factor-kappa B-dependent Genes in Primary Rat Pancreatic beta -Cells J. Biol. Chem., December 21, 2001; 276(52): 48879 - 48886. [Abstract] [Full Text] [PDF]

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