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RelB regulates manganese superoxide dismutase gene and resistance to ionizing radiation of prostate cancer cells

Oncogene volume 25, pages 1554–1559 (2006)Cite this article

Abstract

The relationship between NF-κB and resistance to radiation treatment in many tumor cell types has been generally well recognized. However, which members of the NF-κB family contribute to radiation resistance is unclear. In the present study, we demonstrate that RelB plays an important radioprotective role in aggressive prostate cancer cells, in part by the induction of antioxidant and antiapoptotic manganese superoxide dismutase (MnSOD) gene. RelB is both constitutively present and is inducible by radiation in aggressive prostate cancer cells. Using ectopically expressed dominant negative inhibitor, p100 mutant, and the siRNA approach, we demonstrate that selective inhibition of RelB significantly decreases the levels of MnSOD resulting in a significant increase in the sensitivity of prostate cancer cells to radiation treatment. These results demonstrate that RelB plays an important role in redox regulation of the cell and protects aggressive prostate cancer cells against radiation-induced cell death. Thus, inhibition of RelB could be a novel mechanism to radiosensitize prostate cancer.

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Acknowledgements

We thank Dr Shao-Cong Sun for the p100 mutant plasmid. We are grateful to Dr Ali Meigooni, Professor of Physics in the Department of Radiation Medicine, for the dosimetry and calibration of the X-ray machine. This work was supported by the University of Kentucky Research Foundation and NIH grant CA 49797.

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Authors and Affiliations

  1. Graduate Center for Toxicology, University of Kentucky, Lexington, Kentucky, USA

    S Josson, Y Xu, S K Dhar & D K St Clair

  2. Department of Radiation Medicine, University of Kentucky, Lexington, Kentucky, USA

    F Fang & W H St Clair

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  1. S Josson
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  2. Y Xu
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  3. F Fang
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  4. S K Dhar
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Correspondence to W H St Clair.

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Josson, S., Xu, Y., Fang, F. et al. RelB regulates manganese superoxide dismutase gene and resistance to ionizing radiation of prostate cancer cells. Oncogene 25, 1554–1559 (2006). https://doi.org/10.1038/sj.onc.1209186

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