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  • Title: Myc suppression of Nfkb2 accelerates lymphomagenesis.
    Author: Keller U, Huber J, Nilsson JA, Fallahi M, Hall MA, Peschel C, Cleveland JL.
    Journal: BMC Cancer; 2010 Jul 02; 10():348. PubMed ID: 20598117.
    Abstract:
    BACKGROUND: 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-kappaB, transcription factors that control the immune response, cell survival, and transformation, and that are frequently altered in cancer. The Rel/NF-kappaB family member NFKB2 is altered by chromosomal translocations or deletions in lymphoid malignancies and deletion of the C-terminal ankyrin domain of NF-kappaB2 augments lymphocyte proliferation. METHODS: Precancerous Emicro-Myc-transgenic B cells, Emicro-Myc lymphomas and human Burkitt lymphoma samples were assessed for Nfkb2 expression. The contribution of Nfkb2 to Myc-driven apoptosis, proliferation, and lymphomagenesis was tested genetically in vivo. RESULTS: Here we report that the Myc oncoprotein suppresses Nfkb2 expression in vitro in primary mouse fibroblasts and B cells, and in vivo in the Emicro-Myc transgenic mouse model of human Burkitt lymphoma (BL). NFKB2 suppression by Myc was also confirmed in primary human BL. Promoter-reporter assays indicate that Myc-mediated suppression of Nfkb2 occurs at the level of transcription. The contribution of Nfkb2 to Myc-driven lymphomagenesis was tested in vivo, where Nfkb2 loss was shown to accelerate lymphoma development in Emicro-Myc transgenic mice, by impairing Myc's apoptotic response. CONCLUSIONS: Nfkb2 is suppressed by c-Myc and harnesses Myc-driven lymphomagenesis. These data thus link Myc-driven lymphomagenesis to the non-canonical NF-kappaB pathway.
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