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NF-κB activates Bcl-2 expression in t(14;18) lymphoma cells

Oncogene volume 21, pages 3898–3908 (2002)Cite this article

Abstract

The t(14;18) translocation, which is characteristic of follicular lymphoma, results in the overexpression of the bcl-2 gene dependent upon regulatory elements within the bcl-2 5′ flanking region and the immunoglobulin heavy chain gene enhancers. Conflicting evidence exists on the effects of NF-κB expression on Bcl-2 levels in different cell types. Lymphoma cells with the t(14;18) translocation show high levels of nuclear NF-κB proteins. We observed decreased levels of endogenous Bcl-2 when the IκBα-super-repressor was expressed in a t(14;18) cell line. Deletion analysis of the bcl-2 promoter indicated that the repressive effect of the IκBα-super-repressor occurred through a region that contained no NF-κB consensus sequences. This highly active region contained a c-AMP response element (CRE) and several Sp1 binding sites. Chromatin immunoprecipitation assays with antibodies specific for the NF-κB and CREB/ATF family members, as well as Sp1, resulted in the isolation of this IκBα-super-repressor responsive region of the bcl-2 promoter. Mutation of the CRE and the two Sp1 sites in different combinations in bcl-2 reporter constructs resulted in the loss of bcl-2 promoter repression by the IκBα-super-repressor. We therefore conclude that the activation of bcl-2 by NF-κB in t(14;18) lymphoma cells is mediated through the CRE and Sp1 binding sites.

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Acknowledgements

We gratefully acknowledge Dr Arnold Rabson for kindly providing us with the IκBα-SR expression vector and Dr Peggy Farnham for sharing the ChIP assay protocol. This work was supported by National Institutes of Health Grant CA56764.

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Authors and Affiliations

  1. Center for Molecular Biology in Medicine, Veterans Affairs Palo Alto Health Care System, 94305, California, CA, USA

    Caroline A Heckman, John W Mehew & Linda M Boxer

  2. Department of Medicine, Stanford University School of Medicine, Stanford, 94305, California, CA, USA

    Caroline A Heckman, John W Mehew & Linda M Boxer

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  1. Caroline A Heckman
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Correspondence to Linda M Boxer.

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Heckman, C., Mehew, J. & Boxer, L. NF-κB activates Bcl-2 expression in t(14;18) lymphoma cells. Oncogene 21, 3898–3908 (2002). https://doi.org/10.1038/sj.onc.1205483

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