TY  - JOUR
AU  - Klapproth, Kay
AU  - Sander, Sandrine
AU  - Marinković, Dragan
AU  - Baumann, Bernd
AU  - Wirth, Thomas
PY  - 2009
UR  - http://rfasper.fasper.bg.ac.rs/handle/123456789/309
AB  - Deregulated c-MYC is found in a variety of cancers where it promotes proliferation as well as apoptosis. In many hematologic malignancies, enhanced NF-kappa B exerts prosurvival functions. Here we investigated the role of NF-kappa B in mouse and human c-MYC-transformed lymphomas. The NF-kappa B pathway is extinguished in murine lymphoma cells, and extrinsic stimuli typically inducing NF-kappa B activity fail to activate this pathway. Genetic activation of the NF-kappa B pathway induces apoptosis in these cells, whereas inhibition of NF-kappa B by an I kappa B alpha superrepressor provides a selective advantage in vivo. Furthermore, in human Burkitt lymphoma cells we find that NF-kappa B activation induces apoptosis. NF-kappa B up-regulates Fas and predisposes to Fas-induced cell death, which is caspase-8 mediated and can be prevented by CFLAR overexpression. We conclude that c-MYC overexpression sensitizes cells to NF-kappa B-induced apoptosis, and persistent inactivity of NF-kappa B signaling is a prerequisite for MYC-mediated tumorigenesis. We could also show that low immunogenicity and Fas insensitivity of MYC-driven lymphoma cells are reversed by activation of NF-kappa B. Our observations provide a molecular explanation for the described absence of the NF-kappa B signaling in Burkitt lymphoma and question the applicability of NF-kappa B inhibitors as candidates for treatment of this cancer. (Blood. 2009; 114: 2448-2458)
PB  - Amer Soc Hematology, Washington
T2  - Blood
T1  - The IKK2/NF-kappa B pathway suppresses MYC-induced lymphomagenesis
EP  - 2458
IS  - 12
SP  - 2448
VL  - 114
DO  - 10.1182/blood-2008-09-181008
ER  - 

@article{
author = "Klapproth, Kay and Sander, Sandrine and Marinković, Dragan and Baumann, Bernd and Wirth, Thomas",
year = "2009",
abstract = "Deregulated c-MYC is found in a variety of cancers where it promotes proliferation as well as apoptosis. In many hematologic malignancies, enhanced NF-kappa B exerts prosurvival functions. Here we investigated the role of NF-kappa B in mouse and human c-MYC-transformed lymphomas. The NF-kappa B pathway is extinguished in murine lymphoma cells, and extrinsic stimuli typically inducing NF-kappa B activity fail to activate this pathway. Genetic activation of the NF-kappa B pathway induces apoptosis in these cells, whereas inhibition of NF-kappa B by an I kappa B alpha superrepressor provides a selective advantage in vivo. Furthermore, in human Burkitt lymphoma cells we find that NF-kappa B activation induces apoptosis. NF-kappa B up-regulates Fas and predisposes to Fas-induced cell death, which is caspase-8 mediated and can be prevented by CFLAR overexpression. We conclude that c-MYC overexpression sensitizes cells to NF-kappa B-induced apoptosis, and persistent inactivity of NF-kappa B signaling is a prerequisite for MYC-mediated tumorigenesis. We could also show that low immunogenicity and Fas insensitivity of MYC-driven lymphoma cells are reversed by activation of NF-kappa B. Our observations provide a molecular explanation for the described absence of the NF-kappa B signaling in Burkitt lymphoma and question the applicability of NF-kappa B inhibitors as candidates for treatment of this cancer. (Blood. 2009; 114: 2448-2458)",
publisher = "Amer Soc Hematology, Washington",
journal = "Blood",
title = "The IKK2/NF-kappa B pathway suppresses MYC-induced lymphomagenesis",
pages = "2458-2448",
number = "12",
volume = "114",
doi = "10.1182/blood-2008-09-181008"
}

Klapproth, K., Sander, S., Marinković, D., Baumann, B.,& Wirth, T.. (2009). The IKK2/NF-kappa B pathway suppresses MYC-induced lymphomagenesis. in Blood
Amer Soc Hematology, Washington., 114(12), 2448-2458.
https://doi.org/10.1182/blood-2008-09-181008

Klapproth K, Sander S, Marinković D, Baumann B, Wirth T. The IKK2/NF-kappa B pathway suppresses MYC-induced lymphomagenesis. in Blood. 2009;114(12):2448-2458.
doi:10.1182/blood-2008-09-181008 .

Klapproth, Kay, Sander, Sandrine, Marinković, Dragan, Baumann, Bernd, Wirth, Thomas, "The IKK2/NF-kappa B pathway suppresses MYC-induced lymphomagenesis" in Blood, 114, no. 12 (2009):2448-2458,
https://doi.org/10.1182/blood-2008-09-181008 . .