TY  - JOUR
AU  - Schlee, Martin
AU  - Hoelzel, Michael
AU  - Bernard, Sandra
AU  - Mailhammer, Reinhard
AU  - Schuhmacher, Marino
AU  - Reschke, Judith
AU  - Eick, Dirk
AU  - Marinković, Dragan
AU  - Wirth, Thomas
AU  - Rosenwald, Andreas
AU  - Staudt, Louis M.
AU  - Eilers, Martin
AU  - Baran-Marszak, Fanny
AU  - Fagard, Remi
AU  - Feuillard, Jean
AU  - Laux, Gerhard
AU  - Bornkamm, Georg W.
PY  - 2007
UR  - http://rfasper.fasper.bg.ac.rs/handle/123456789/119
AB  - 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-kappa 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-H 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.
PB  - Wiley-Liss, Hoboken
T2  - International Journal of Cancer
T1  - c-MYC activation impairs the NF-kappa B and the interferon response: Implications for the pathogenesis of Burkitt's lymphoma
EP  - 1395
IS  - 7
SP  - 1387
VL  - 120
DO  - 10.1002/ijc.22372
ER  - 

@article{
author = "Schlee, Martin and Hoelzel, Michael and Bernard, Sandra and Mailhammer, Reinhard and Schuhmacher, Marino and Reschke, Judith and Eick, Dirk and Marinković, Dragan and Wirth, Thomas and Rosenwald, Andreas and Staudt, Louis M. and Eilers, Martin and Baran-Marszak, Fanny and Fagard, Remi and Feuillard, Jean and Laux, Gerhard and Bornkamm, Georg W.",
year = "2007",
abstract = "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-kappa 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-H 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.",
publisher = "Wiley-Liss, Hoboken",
journal = "International Journal of Cancer",
title = "c-MYC activation impairs the NF-kappa B and the interferon response: Implications for the pathogenesis of Burkitt's lymphoma",
pages = "1395-1387",
number = "7",
volume = "120",
doi = "10.1002/ijc.22372"
}

Schlee, M., Hoelzel, M., Bernard, S., Mailhammer, R., Schuhmacher, M., Reschke, J., Eick, D., Marinković, D., Wirth, T., Rosenwald, A., Staudt, L. M., Eilers, M., Baran-Marszak, F., Fagard, R., Feuillard, J., Laux, G.,& Bornkamm, G. W.. (2007). c-MYC activation impairs the NF-kappa B and the interferon response: Implications for the pathogenesis of Burkitt's lymphoma. in International Journal of Cancer
Wiley-Liss, Hoboken., 120(7), 1387-1395.
https://doi.org/10.1002/ijc.22372

Schlee M, Hoelzel M, Bernard S, Mailhammer R, Schuhmacher M, Reschke J, Eick D, Marinković D, Wirth T, Rosenwald A, Staudt LM, Eilers M, Baran-Marszak F, Fagard R, Feuillard J, Laux G, Bornkamm GW. c-MYC activation impairs the NF-kappa B and the interferon response: Implications for the pathogenesis of Burkitt's lymphoma. in International Journal of Cancer. 2007;120(7):1387-1395.
doi:10.1002/ijc.22372 .

Schlee, Martin, Hoelzel, Michael, Bernard, Sandra, Mailhammer, Reinhard, Schuhmacher, Marino, Reschke, Judith, Eick, Dirk, Marinković, Dragan, Wirth, Thomas, Rosenwald, Andreas, Staudt, Louis M., Eilers, Martin, Baran-Marszak, Fanny, Fagard, Remi, Feuillard, Jean, Laux, Gerhard, Bornkamm, Georg W., "c-MYC activation impairs the NF-kappa B and the interferon response: Implications for the pathogenesis of Burkitt's lymphoma" in International Journal of Cancer, 120, no. 7 (2007):1387-1395,
https://doi.org/10.1002/ijc.22372 . .