SEARCH:   Advanced

This Article Full Text Full Text (PDF) 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 Hinz, M. Articles by Scheidereit, C. Search for Related Content PubMed PubMed Citation Articles by Hinz, M. Articles by Scheidereit, C. 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: B. K. Bednarski, X. Ding, K. Coombe, A. S. Baldwin, and H. J. Kim Active roles for inhibitory {kappa}B kinases {alpha} and {beta} in nuclear factor-{kappa}B-mediated chemoresistance to doxorubicin Mol. Cancer Ther., July 1, 2008; 7(7): 1827 - 1835. [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. Bortezomib and gemcitabine in relapsed or refractory Hodgkin's lymphoma Ann. Onc., May 25, 2008; (2008) mdn365v1. [Abstract] [Full Text] [PDF] T. Alvaro, M. Lejeune, J. F. Garcia, Ma. T. Salvado, C. Lopez, R. Bosch, J. Jaen, P. Escriva, and L. E. Pons Tumor-Infiltrated Immune Response Correlates with Alterations in the Apoptotic and Cell Cycle Pathways in Hodgkin and Reed-Sternberg Cells Clin. Cancer Res., February 1, 2008; 14(3): 685 - 691. [Abstract] [Full Text] [PDF] B. Hirsch, M. Hummel, S. Bentink, F. Fouladi, R. Spang, R. Zollinger, H. Stein, and H. Durkop CD30-Induced Signaling Is Absent in Hodgkin's Cells but Present in Anaplastic Large Cell Lymphoma Cells Am. J. Pathol., February 1, 2008; 172(2): 510 - 520. [Abstract] [Full Text] [PDF] V. Stagni, M. G. di Bari, S. Cursi, I. Condo, M. T. Cencioni, R. Testi, Y. Lerenthal, E. Cundari, and D. Barila ATM kinase activity modulates Fas sensitivity through the regulation of FLIP in lymphoid cells Blood, January 15, 2008; 111(2): 829 - 837. [Abstract] [Full Text] [PDF] K. Bunting, S. Rao, K. Hardy, D. Woltring, G. S. Denyer, J. Wang, S. Gerondakis, and M. F. Shannon Genome-Wide Analysis of Gene Expression in T Cells to Identify Targets of the NF-{kappa}B Transcription Factor c-Rel J. Immunol., June 1, 2007; 178(11): 7097 - 7109. [Abstract] [Full Text] [PDF] A. Chiu, W. Xu, B. He, S. R. Dillon, J. A. Gross, E. Sievers, X. Qiao, P. Santini, E. Hyjek, J.-w. Lee, et al. Hodgkin lymphoma cells express TACI and BCMA receptors and generate survival and proliferation signals in response to BAFF and APRIL Blood, January 15, 2007; 109(2): 729 - 739. [Abstract] [Full Text] [PDF] G. Penna, S. Amuchastegui, N. Giarratana, K. C. Daniel, M. Vulcano, S. Sozzani, and L. Adorini 1,25-Dihydroxyvitamin D3 Selectively Modulates Tolerogenic Properties in Myeloid but Not Plasmacytoid Dendritic Cells J. Immunol., January 1, 2007; 178(1): 145 - 153. [Abstract] [Full Text] [PDF] A. Ushmorov, F. Leithauser, O. Sakk, A. Weinhausel, S. W. Popov, P. Moller, and T. Wirth Epigenetic processes play a major role in B-cell-specific gene silencing in classical Hodgkin lymphoma Blood, March 15, 2006; 107(6): 2493 - 2500. [Abstract] [Full Text] [PDF] F. Feuerhake, J. L. Kutok, S. Monti, W. Chen, A. S. LaCasce, G. Cattoretti, P. Kurtin, G. S. Pinkus, L. de Leval, N. L. Harris, et al. NF{kappa}B activity, function, and target-gene signatures in primary mediastinal large B-cell lymphoma and diffuse large B-cell lymphoma subtypes Blood, August 15, 2005; 106(4): 1392 - 1399. [Abstract] [Full Text] [PDF] S. J. Sup, C. A. Alemany, B. Pohlman, P. Elson, S. Malhi, S. Thakkar, R. Steinle, and E. D. Hsi Expression of bcl-2 in Classical Hodgkin's Lymphoma: An Independent Predictor of Poor Outcome J. Clin. Oncol., June 1, 2005; 23(16): 3773 - 3779. [Abstract] [Full Text] [PDF] M. E. Moreno-Garcia, L. N. Lopez-Bojorques, A. Zentella, L. A. Humphries, D. J. Rawlings, and L. Santos-Argumedo CD38 Signaling Regulates B Lymphocyte Activation via a Phospholipase C (PLC)-{gamma}2-Independent, Protein Kinase C, Phosphatidylcholine-PLC, and Phospholipase D-Dependent Signaling Cascade J. Immunol., March 1, 2005; 174(5): 2687 - 2695. [Abstract] [Full Text] [PDF] M. Mandal, C. Borowski, T. Palomero, A. A. Ferrando, P. Oberdoerffer, F. Meng, A. Ruiz-Vela, M. Ciofani, J.-C. Zuniga-Pflucker, I. Screpanti, et al. The BCL2A1 gene as a pre-T cell receptor-induced regulator of thymocyte survival J. Exp. Med., February 22, 2005; 201(4): 603 - 614. [Abstract] [Full Text] [PDF] L. T. Lam, R. E. Davis, J. Pierce, M. Hepperle, Y. Xu, M. Hottelet, Y. Nong, D. Wen, J. Adams, L. Dang, et al. Small Molecule Inhibitors of I{kappa}B Kinase Are Selectively Toxic for Subgroups of Diffuse Large B-Cell Lymphoma Defined by Gene Expression Profiling Clin. Cancer Res., January 1, 2005; 11(1): 28 - 40. [Abstract] [Full Text] [PDF] Y. X. Zhu, S. Benn, Z. H. Li, E. Wei, E. Masih-Khan, Y. Trieu, M. Bali, C. J. McGlade, J. O. Claudio, and A. K. Stewart The SH3-SAM Adaptor HACS1 is Up-regulated in B Cell Activation Signaling Cascades J. Exp. Med., September 20, 2004; 200(6): 737 - 747. [Abstract] [Full Text] [PDF] A. Loercher, T. L. Lee, J. L. Ricker, A. Howard, J. Geoghegen, Z. Chen, J. B. Sunwoo, R. Sitcheran, E. Y. Chuang, J. B. Mitchell, et al. Nuclear Factor-{kappa}B is an Important Modulator of the Altered Gene Expression Profile and Malignant Phenotype in Squamous Cell Carcinoma Cancer Res., September 15, 2004; 64(18): 6511 - 6523. [Abstract] [Full Text] [PDF] C. Montalban, J. F. Garcia, V. Abraira, L. Gonzalez-Camacho, M. M. Morente, J. L. Bello, E. Conde, M. A. Cruz, R. Garcia-Sanz, J. Garcia-Larana, et al. Influence of Biologic Markers on the Outcome of Hodgkin's Lymphoma: A Study by the Spanish Hodgkin's Lymphoma Study Group J. Clin. Oncol., May 1, 2004; 22(9): 1664 - 1673. [Abstract] [Full Text] [PDF] S. Mathas, A. Lietz, I. Anagnostopoulos, F. Hummel, B. Wiesner, M. Janz, F. Jundt, B. Hirsch, K. Johrens-Leder, H.-P. Vornlocher, et al. c-FLIP Mediates Resistance of Hodgkin/Reed-Sternberg Cells to Death Receptor-induced Apoptosis J. Exp. Med., April 19, 2004; 199(8): 1041 - 1052. [Abstract] [Full Text] [PDF] A. Sanchez-Aguilera, J. Delgado, F. I. Camacho, M. Sanchez-Beato, L. Sanchez, C. Montalban, M. F. Fresno, C. Martin, M. A. Piris, and J. F. Garcia Silencing of the p18INK4c gene by promoter hypermethylation in Reed-Sternberg cells in Hodgkin lymphomas Blood, March 15, 2004; 103(6): 2351 - 2357. [Abstract] [Full Text] [PDF] G.J.S. Jenkins, K. Harries, S.H. Doak, A. Wilmes, A.P. Griffiths, J.N. Baxter, and J.M. Parry The bile acid deoxycholic acid (DCA) at neutral pH activates NF-{kappa}B and induces IL-8 expression in oesophageal cells in vitro Carcinogenesis, March 1, 2004; 25(3): 317 - 323. [Abstract] [Full Text] [PDF] E. T. Chang, T. Zheng, E. G. Weir, M. Borowitz, R. B. Mann, D. Spiegelman, and N. E. Mueller Aspirin and the Risk of Hodgkin's Lymphoma in a Population-Based Case-Control Study J Natl Cancer Inst, February 18, 2004; 96(4): 305 - 315. [Abstract] [Full Text] [PDF] G. Jin, A. Klika, M. Callahan, B. Faga, J. Danzig, Z. Jiang, X. Li, G. R. Stark, J. Harrington, and B. Sherf Identification of a human NF-{kappa}B-activating protein, TAB3 PNAS, February 17, 2004; 101(7): 2028 - 2033. [Abstract] [Full Text] [PDF] A.-I. Saez, A.-J. Saez, M.-J. Artiga, A. Perez-Rosado, F.-I. Camacho, A. Diez, J.-F. Garcia, M. Fraga, R. Bosch, S.-M. Rodriguez-Pinilla, et al. Building an Outcome Predictor Model for Diffuse Large B-Cell Lymphoma Am. J. Pathol., February 1, 2004; 164(2): 613 - 622. [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]