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Myc suppression of Nfkb2 accelerates lymphomagenesis
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-κB, transcription factors that control the immune response, cell survival, and transfor...
Autores principales: | , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2010
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2902445/ https://www.ncbi.nlm.nih.gov/pubmed/20598117 http://dx.doi.org/10.1186/1471-2407-10-348 |
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author | Keller, Ulrich Huber, Jürgen Nilsson, Jonas A Fallahi, Mohammad Hall, Mark A Peschel, Christian Cleveland, John L |
author_facet | Keller, Ulrich Huber, Jürgen Nilsson, Jonas A Fallahi, Mohammad Hall, Mark A Peschel, Christian Cleveland, John L |
author_sort | Keller, Ulrich |
collection | PubMed |
description | 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-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 NFKB2 is altered by chromosomal translocations or deletions in lymphoid malignancies and deletion of the C-terminal ankyrin domain of NF-κB2 augments lymphocyte proliferation. METHODS: Precancerous Eμ-Myc-transgenic B cells, Eμ-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 Eμ-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 Eμ-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-κB pathway. |
format | Text |
id | pubmed-2902445 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-29024452010-07-13 Myc suppression of Nfkb2 accelerates lymphomagenesis Keller, Ulrich Huber, Jürgen Nilsson, Jonas A Fallahi, Mohammad Hall, Mark A Peschel, Christian Cleveland, John L BMC Cancer Research Article 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-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 NFKB2 is altered by chromosomal translocations or deletions in lymphoid malignancies and deletion of the C-terminal ankyrin domain of NF-κB2 augments lymphocyte proliferation. METHODS: Precancerous Eμ-Myc-transgenic B cells, Eμ-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 Eμ-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 Eμ-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-κB pathway. BioMed Central 2010-07-02 /pmc/articles/PMC2902445/ /pubmed/20598117 http://dx.doi.org/10.1186/1471-2407-10-348 Text en Copyright ©2010 Keller et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Keller, Ulrich Huber, Jürgen Nilsson, Jonas A Fallahi, Mohammad Hall, Mark A Peschel, Christian Cleveland, John L Myc suppression of Nfkb2 accelerates lymphomagenesis |
title | Myc suppression of Nfkb2 accelerates lymphomagenesis |
title_full | Myc suppression of Nfkb2 accelerates lymphomagenesis |
title_fullStr | Myc suppression of Nfkb2 accelerates lymphomagenesis |
title_full_unstemmed | Myc suppression of Nfkb2 accelerates lymphomagenesis |
title_short | Myc suppression of Nfkb2 accelerates lymphomagenesis |
title_sort | myc suppression of nfkb2 accelerates lymphomagenesis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2902445/ https://www.ncbi.nlm.nih.gov/pubmed/20598117 http://dx.doi.org/10.1186/1471-2407-10-348 |
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