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Myc suppression of ...
Myc suppression of Nfkb2 accelerates lymphomagenesis
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Keller, Ulrich (författare)
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Huber, Juergen (författare)
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- Nilsson, Jonas A. (författare)
- Umeå universitet,Institutionen för molekylärbiologi (Medicinska fakulteten),St Jude Childrens Hosp, Dept Biochem, Memphis, TN 38105 USA
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Fallahi, Mohammad (författare)
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Hall, Mark A. (författare)
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Peschel, Christian (författare)
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Cleveland, John L. (författare)
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(creator_code:org_t)
- 2010-07-02
- 2010
- Engelska.
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 10
- Relaterad länk:
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https://doi.org/10.1...
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https://umu.diva-por... (primary) (Raw object)
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https://bmccancer.bi...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
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- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
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