The IKK2/NF-kappa B pathway suppresses MYC-induced lymphomagenesis
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2009
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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 s...ignaling 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)
Izvor:
Blood, 2009, 114, 12, 2448-2458Izdavač:
- Amer Soc Hematology, Washington
DOI: 10.1182/blood-2008-09-181008
ISSN: 0006-4971
PubMed: 19628709
WoS: 000269925000013
Scopus: 2-s2.0-70350506572
Institucija/grupa
rFASPERTY - 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 . .