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Regulation of Bcl-2 expression by C/EBP in t(14;18) lymphoma cells

Oncogene volume 22, pages 7891–7899 (2003)Cite this article

Abstract

In follicular lymphomas with the t(14;18) translocation, there is increased expression of the bcl-2 gene, which is dependent upon regulatory elements within the bcl-2 5′ flanking region and the immunoglobulin heavy-chain gene enhancers. We found that t(14;18) lymphomas expressed C/EBPα, which is not normally expressed in B lymphocytes. Expression of C/EBPα increased bcl-2 expression, and two regions of the bcl-2 P2 promoter that mediated this effect were identified. C/EBPβ was also able to increase bcl-2 promoter activity through these sites. The 5′ site was GC-rich and did not contain a C/EBP consensus sequence; however, C/EBP was observed to interact with this site both in vitro by EMSA and in vivo by chromatin immunoprecipitation assay. The 3′ region contained the Cdx site, which mediates the effect of A-Myb on the bcl-2 promoter. In vivo binding studies revealed that C/EBP interacted with this region of the bcl-2 promoter as well. Decreased expression of C/EBP factors due to targeting of their transcripts by siRNA molecules resulted in downregulation of Bcl-2 protein. We conclude that C/EBPα and C/EBPβ contribute to the deregulated expression of Bcl-2 in t(14;18) lymphoma cells.

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Acknowledgements

We gratefully acknowledge the assistance of Cathy Crumpton and Lusijah Rott of the Stanford University Digestive Disease Center Flow Cytometry Facility. Dr Gretchen Darlington kindly provided the human C/EBPα cDNA, and Dr Branimir Sikic provided the C/EBPβ expression vector. 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, Palo Alto, 94304, CA, USA

    Caroline A Heckman, Melissa A Wheeler & Linda M Boxer

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

    Caroline A Heckman, Melissa A Wheeler & Linda M Boxer

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  1. Caroline A Heckman
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  2. Melissa A Wheeler
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  3. Linda M Boxer
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Correspondence to Linda M Boxer.

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Heckman, C., Wheeler, M. & Boxer, L. Regulation of Bcl-2 expression by C/EBP in t(14;18) lymphoma cells. Oncogene 22, 7891–7899 (2003). https://doi.org/10.1038/sj.onc.1206639

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