| Summary: | <p>Abstract</p> <p>Background</p> <p>Deregulated c-Myc expression is a hallmark of several human cancers where it promotes proliferation and an aggressive tumour phenotype. Myc overexpression is associated with reduced activity of Rel/NF-κB, transcription factors that control the immune response, cell survival, and transformation, and that are frequently altered in cancer. The Rel/NF-κB family member <it>NFKB2 </it>is altered by chromosomal translocations or deletions in lymphoid malignancies and deletion of the <it>C</it>-terminal ankyrin domain of NF-κB2 augments lymphocyte proliferation.</p> <p>Methods</p> <p>Precancerous Eμ-<it>Myc</it>-transgenic B cells, Eμ-<it>Myc </it>lymphomas and human Burkitt lymphoma samples were assessed for <it>Nfkb2 </it>expression. The contribution of <it>Nfkb2 </it>to Myc-driven apoptosis, proliferation, and lymphomagenesis was tested genetically in vivo.</p> <p>Results</p> <p>Here we report that the Myc oncoprotein suppresses <it>Nfkb2 </it>expression in vitro in primary mouse fibroblasts and B cells, and in vivo in the Eμ-<it>Myc </it>transgenic mouse model of human Burkitt lymphoma (BL). <it>NFKB2 </it>suppression by Myc was also confirmed in primary human BL. Promoter-reporter assays indicate that Myc-mediated suppression of <it>Nfkb2 </it>occurs at the level of transcription. The contribution of <it>Nfkb2 </it>to Myc-driven lymphomagenesis was tested in vivo, where <it>Nfkb2 </it>loss was shown to accelerate lymphoma development in Eμ-<it>Myc </it>transgenic mice, by impairing Myc's apoptotic response.</p> <p>Conclusions</p> <p><it>Nfkb2 </it>is suppressed by c-Myc and harnesses Myc-driven lymphomagenesis. These data thus link Myc-driven lymphomagenesis to the non-canonical NF-κB pathway.</p>
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