Nuclear Factor κB–dependent Gene Expression Profiling of Hodgkin's Disease Tumor Cells, Pathogenetic Significance, and Link to Constitutive Signal Transducer and Activator of Transcription 5a Activity
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- Michael Hinz
- 1Max-Delbrück Center for Molecular Medicine, 13125 Berlin, Germany
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- Petra Lemke
- 1Max-Delbrück Center for Molecular Medicine, 13125 Berlin, Germany
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- Ioannis Anagnostopoulos
- 2Institute for Pathology, Universitätsklinikum Benjamin Franklin, Free University, 12200 Berlin, Germany
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- Christine Hacker
- 1Max-Delbrück Center for Molecular Medicine, 13125 Berlin, Germany
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- Daniel Krappmann
- 1Max-Delbrück Center for Molecular Medicine, 13125 Berlin, Germany
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- Stephan Mathas
- 1Max-Delbrück Center for Molecular Medicine, 13125 Berlin, Germany
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- Bernd Dörken
- 1Max-Delbrück Center for Molecular Medicine, 13125 Berlin, Germany
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- Martin Zenke
- 1Max-Delbrück Center for Molecular Medicine, 13125 Berlin, Germany
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- Harald Stein
- 2Institute for Pathology, Universitätsklinikum Benjamin Franklin, Free University, 12200 Berlin, Germany
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- Claus Scheidereit
- 1Max-Delbrück Center for Molecular Medicine, 13125 Berlin, Germany
抄録
<jats:p>Constitutive nuclear nuclear factor (NF)-κB activity is observed in a variety of hematopoietic and solid tumors. Given the distinctive role of constitutive NF-κB for Hodgkin and Reed-Sternberg (HRS) cell viability, we performed molecular profiling in two Hodgkin's disease (HD) cell lines to identify NF-κB target genes. We recognized 45 genes whose expression in both cell lines was regulated by NF-κB. The NF-κB–dependent gene profile comprises chemokines, cytokines, receptors, apoptotic regulators, intracellular signaling molecules, and transcription factors, the majority of which maintain a marker-like expression in HRS cells. Remarkably, we found 17 novel NF-κB target genes. Using chromatin immunoprecipitation we demonstrate that NF-κB is recruited directly to the promoters of several target genes, including signal transducer and activator of transcription (STAT)5a, interleukin-13, and CC chemokine receptor 7. Intriguingly, NF-κB positively regulates STAT5a expression and signaling pathways in HRS cells, and promotes its persistent activation. In fact, STAT5a overexpression was found in most tumor cells of tested patients with classical HD, indicating a critical role for HD. The gene profile underscores a central role of NF-κB in the pathogenesis of HD and potentially of other tumors with constitutive NF-κB activation.</jats:p>
収録刊行物
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- The Journal of Experimental Medicine
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The Journal of Experimental Medicine 196 (5), 605-617, 2002-08-26
Rockefeller University Press
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詳細情報 詳細情報について
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- CRID
- 1363107369991503744
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- NII論文ID
- 30017416832
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- ISSN
- 15409538
- 00221007
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