RelB regulates manganese superoxide dismutase gene and resistance to ionizing radiation of prostate cancer cells.
The relationship between NF-kappaB and resistance to radiation treatment in many tumor cell types has been generally well recognized. However, which members of the NF-kappaB 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.
Josson
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S
Graduate Center for Toxicology, University of Kentucky, Lexington, Kentucky 40536, USA.
Xu
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Y
Fang
F
F
Dhar
S K
SK
St Clair
D K
DK
St Clair
W H
WH
D004790:Enzyme Induction / Q000528:radiation effects; D005720:Gamma Rays; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects*; D006801:Humans; D008297:Male; D018384:Oxidative Stress / Q000528:radiation effects; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000532:radiotherapy*; D012333:RNA, Messenger / Q000378:metabolism; D011836:Radiation Tolerance; D013482:Superoxide Dismutase / Q000096:biosynthesis / Q000235:genetics* / Q000528:radiation effects; D051841:Transcription Factor RelB / Q000037:antagonists & inhibitors / Q000502:physiology* / Q000528:radiation effects
C497593:RELB protein, human; D012333:RNA, Messenger; D051841:Transcription Factor RelB; D013482:Superoxide Dismutase