Send to

Choose Destination
See comment in PubMed Commons below
Blood. 2009 Sep 17;114(12):2448-58. doi: 10.1182/blood-2008-09-181008. Epub 2009 Jul 23.

The IKK2/NF-{kappa}B pathway suppresses MYC-induced lymphomagenesis.

Author information

  • 1Institute of Physiological Chemistry, University of Ulm, Germany.


Deregulated c-MYC is found in a variety of cancers where it promotes proliferation as well as apoptosis. In many hematologic malignancies, enhanced NF-kappaB exerts prosurvival functions. Here we investigated the role of NF-kappaB in mouse and human c-MYC-transformed lymphomas. The NF-kappaB pathway is extinguished in murine lymphoma cells, and extrinsic stimuli typically inducing NF-kappaB activity fail to activate this pathway. Genetic activation of the NF-kappaB pathway induces apoptosis in these cells, whereas inhibition of NF-kappaB by an IkappaBalpha superrepressor provides a selective advantage in vivo. Furthermore, in human Burkitt lymphoma cells we find that NF-kappaB activation induces apoptosis. NF-kappaB 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-kappaB-induced apoptosis, and persistent inactivity of NF-kappaB 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-kappaB. Our observations provide a molecular explanation for the described absence of the NF-kappaB signaling in Burkitt lymphoma and question the applicability of NF-kappaB inhibitors as candidates for treatment of this cancer.

[PubMed - indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire
    Loading ...
    Support Center