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Oct transcription factors mediate t(14;18) lymphoma cell survival by directly regulating bcl-2 expression

Oncogene volume 25, pages 888–898 (2006)Cite this article

Abstract

Oct-1 and Oct-2 are members of the POU homeodomain family of transcriptional regulators and are critical for normal embryonic development. Gene-targeting studies showed that Oct-1 and Oct-2 are largely dispensable for B-cell development and immunoglobulin production, although both Oct-2 and Bob-1 are required for a proper immune response and germinal center formation. In these studies, we investigated the role of Oct factors in B-cell lymphomas. Recent investigations have shown increased expression of Oct-2 and Bob-1 in lymphomas, and we observed greatly increased levels of Oct-2 in lymphoma cells with the t(14;18) translocation. Decreased expression of Oct-1, Oct-2, or Bob-1 by RNA interference resulted in apoptosis and down-regulation of bcl-2 expression. Furthermore, Oct-2 induced bcl-2 promoter activity and mediated this effect through three regions in the bcl-2 P2 promoter. Although these regions did not contain canonical octamer motifs, we observed the direct interaction of Oct-2 with all three sites both in vitro by EMSA and in vivo by chromatin immunoprecipitation assay. Moreover, by mutation analysis we found that the ability of Oct-2 to activate bcl-2 required C/EBP, Cdx, and TATA-binding sites. Oct-2, therefore, acts as a cell survival factor in t(14;18) lymphoma cells by directly activating the antiapoptotic gene bcl-2.

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Acknowledgements

We gratefully acknowledge the assistance of Lusijah Rott and Cathy Crumpton of the Stanford University Digestive Disease Center Flow Cytometry Facility. We thank Minh Ho and John Mehew for technical assistance. The Oct-1 and Oct-2 expression vectors were kindly provided by Dr Daniel Tenen through Dr Masahiko Tanaka. Dr Winship Herr generously provided the Bob-1 expression vector. The DHL-6 cells were provided to us by Dr Ronald Levy. This work was supported by the National Institutes of Health Grant CA56764.

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  1. Center for Molecular Biology in Medicine, Palo Alto VAHCS, Palo Alto, CA, USA

    C A Heckman, H Duan, P B Garcia & L M Boxer

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

    C A Heckman, H Duan, P B Garcia & L M Boxer

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  1. C A Heckman
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Correspondence to L M Boxer.

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Heckman, C., Duan, H., Garcia, P. et al. Oct transcription factors mediate t(14;18) lymphoma cell survival by directly regulating bcl-2 expression. Oncogene 25, 888–898 (2006). https://doi.org/10.1038/sj.onc.1209127

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