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Schlee, M. ; Hölzel, M. ; Bernard, S.* ; Mailhammer, R. ; Schuhmacher, M.* ; Reschke, J. ; Eick, D. ; Marinkovic, D.* ; Wirth, T.* ; Rosenwald, A.* ; Staudt, L.M.* ; Eilers, M.* ; Baran-Marszak, F.* ; Fagard, R.* ; Feuillard, J.* ; Laux, G. ; Bornkamm, G.W.

c-MYC activation impairs the NF-kappaB and the interferon response: Implications for the pathogenesis of Burkitt's lymphoma.

Int. J. Cancer 120, 1387-1395 (2007)
DOI
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Deregulation of the proto-oncogene c-myc is a key event in the pathogenesis of many tumors. A paradigm is the activation of the c-myc gene by chromosomal translocations in Burkitt lymphoma (BL). Despite expression of a restricted set of Epstein-Barr viral (EBV) antigens, BL cells are not recognized by antigen-specific cytotoxic T cells (CTLs) because of their inability to process and present HLA class I-restricted antigens. In contrast, cells of EBV-driven posttransplant lymphoproliferative disease (PTLD) are recognized and rejected by EBV-specific CTLs. It is not known whether the poor immunogenicity of BL cells is due to nonexpression of viral antigens, overexpression of c-myc, or both. To understand the basis for immune recognition and escape, we have compared the mRNA expression profiles of BL and EBV-immortalized cells (as PTLD model). Among the genes expressed at low level in BL cells, we have identified many genes involved in the NF-B and interferon response that play a pivotal role in antigen presentation and immune recognition. Using a cell line in which EBNA2 and c-myc can be regulated at will, we show that c-MYC negatively regulates STAT1, the central player linking the Type-I and Type-II interferon response. Switching off c-myc expression leads to STAT1 induction through a direct and indirect mechanism involving induction of Type-I interferons. c-MYC thus masks an interferon-inducing activity in these cells. Our findings imply that immune escape of tumor cells is not only a matter of in vivo selection but may be additionally promoted by activation of a cellular oncogene. © 2007 Wiley-Liss, Inc.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Burkitt's lymphoma; c-myc; STAT1; interferon; NF-B; antigen presentation
ISSN (print) / ISBN 0020-7136
e-ISSN 1097-0215
Zeitschrift International Journal of Cancer
Quellenangaben Band: 120, Heft: 7, Seiten: 1387-1395 Artikelnummer: , Supplement: ,
Verlag Wiley
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Clinical Molecular Biology and Tumor Genetics (K.MOLBI)