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  • Original Paper
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Nfkb1 is dispensable for Myc-induced lymphomagenesis

Oncogene volume 24, pages 6231–6240 (2005)Cite this article

Abstract

Rel/NF-κB transcription factors are critical arbiters of immune responses, cell survival, and transformation, and are frequently deregulated in cancer. The p50 NF-κB1 component of Rel/NF-κB DNA-binding dimers regulates genes involved in both cell cycle traverse and apoptosis. Nfkb1 loss accelerates B cell growth and leads to increased B cell turnover in vivo, phenotypes akin to those manifested in B cells of Eμ-Myc transgenic mice, a model of human Burkitt lymphoma. Interestingly, Eμ-Myc B cells express reduced levels of cytoplasmic and nuclear NF-κB1 and have reduced Rel/NF-κB DNA-binding activity, suggesting that Myc-mediated repression of NF-κB1 might mediate its proliferative and apoptotic effects on B cells. Furthermore, Nfkb1 expression was reduced in the majority of Eμ-Myc lymphomas and was also suppressed in human Burkitt lymphoma. Nonetheless, loss of Nfkb1 did not appreciably affect Myc's proliferative or apoptotic responses in B cells and had no effect on lymphoma development in Eμ-Myc mice. Therefore, Nfkb1 is dispensable for Myc-induced lymphomagenesis.

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Acknowledgements

We thank Sara Norton, Chunying Yang and Elsie White for expert technical assistance. We also thank Mihaela Onciu and John Sandlund for providing samples from Burkitt lymphoma patients, the Animal Resource Center, the Hartwell Center and the FACS Core Facility of St Jude Children's Research Hospital. This work was supported by NIH Grant CA76379 (JLC), the Cancer Center (CORE) support Grant CA21765 and by the American Lebanese Syrian Associated Charities (ALSAC) of St Jude Children's Research Hospital. UK was supported by the Deutsche Forschungsgemeinschaft (grant KE222/5-1). JBO was supported by NRSA Grant F32 CA099478, and JAN is the recipient of the George J Mitchell endowed fellowship from ALSAC.

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  1. Jonas A Nilsson

    Present address: Department of Molecular Biology, Umeå University, SE-901 87, Umeå, Sweden

Authors and Affiliations

  1. Department of Biochemistry, St Jude Children's Research Hospital, 332 N. Lauderdale, Memphis, 38105, TN, USA

    Ulrich Keller, Jonas A Nilsson, Kirsteen H Maclean, Jennifer B Old & John L Cleveland

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Correspondence to John L Cleveland.

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Keller, U., Nilsson, J., Maclean, K. et al. Nfkb1 is dispensable for Myc-induced lymphomagenesis. Oncogene 24, 6231–6240 (2005). https://doi.org/10.1038/sj.onc.1208779

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