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Myc suppression of Nfkb2 accelerates lymphomagenesis
Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). St Jude Childrens Hosp, Dept Biochem, Memphis, TN 38105 USA.
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2010 (English)In: BMC Cancer, ISSN 1471-2407, Vol. 10, 348Article in journal (Refereed) Published
Abstract [en]

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-kappa B, transcription factors that control the immune response, cell survival, and transformation, and that are frequently altered in cancer. The Rel/NF-kappa B family member NFKB2 is altered by chromosomal translocations or deletions in lymphoid malignancies and deletion of the C-terminal ankyrin domain of NF-kappa B2 augments lymphocyte proliferation. Methods: Precancerous E mu-Myc-transgenic B cells, E mu-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 E mu-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 E mu-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-kappa B pathway.

Place, publisher, year, edition, pages
2010. Vol. 10, 348
National Category
Cancer and Oncology
URN: urn:nbn:se:umu:diva-109616DOI: 10.1186/1471-2407-10-348ISI: 000279798400001PubMedID: 20598117OAI: diva2:858636
Available from: 2015-10-02 Created: 2015-10-02 Last updated: 2015-10-02Bibliographically approved

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