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Transcriptional regulation of bcl-2 by nuclear factor κB and its significance in prostate cancer

Oncogene volume 20, pages 7342–7351 (2001)Cite this article

Abstract

This work presents direct evidence that the bcl-2 gene is transcriptionally regulated by nuclear factor-κB (NF-κB) and directly links the TNF-α/NF-κB signaling pathway with Bcl-2 expression and its pro-survival response in human prostate carcinoma cells. DNase I footprinting, gel retardation and supershift analysis identified a NF-κB site in the bcl-2 p2 promoter. In the context of a minimal promoter, this bcl-2 p2 site 1 increased transcription 10-fold in the presence of the p50/p65 expression vectors, comparable to the increment observed with the consensus NF-κB site, while for the full p2 promoter region transcriptional activity was increased sixfold by over-expression of NF-κB, an effect eliminated by mutating the bcl-2 p2 site 1. The expression of Bcl-2 has been linked to the hormone-resistant phenotype of advanced prostate cancer. Here we show that an increase in the level of expression of Bcl-2 in the human prostate carcinoma cell line LNCaP observed in response to hormone withdrawal is further augmented by TNF-α treatment, and this effect is abated by inhibitors of NF-κB. Concomitantly, bcl-2 p2 promoter studies in LNCaP cells show a 40-fold increase in promoter activity after stimulation with TNF-α in the absence of hormone.

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Acknowledgements

This work was supported in part by USPHS grant AI-44434, the Stein Endowment Fund, and the Skaggs training grant. We wish to thank Julie M Ruedi for technical assistance and Carol Fedoryszyn for help with the preparation of this manuscript. PC Atterton supplied technical writing services.

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  1. Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, California, USA

    Sergio D Catz & Jennifer L Johnson

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Correspondence to Jennifer L Johnson.

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Catz, S., Johnson, J. Transcriptional regulation of bcl-2 by nuclear factor κB and its significance in prostate cancer. Oncogene 20, 7342–7351 (2001). https://doi.org/10.1038/sj.onc.1204926

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