RelB regulates manganese superoxide dismutase gene and resistance to ionizing radiation of prostate cancer cells.
Radiation therapy is in the front line for treatment of localized prostate cancer. However, a significant percentage of patients have radiation-resistant disease. The NF-kappaB pathway is an important factor for radiation resistance, and the classical (canonical) pathway is thought to confer protection of prostate cancer cells from ionizing radiation. Recently, the alternative (non-canonical) pathway, which is involved in prostate cancer aggressiveness, has also been shown to be important for radiation resistance in prostate cancer. The alternative NF-kappaB pathway component RelB protects prostate cancer cells from the detrimental effects of ionizing radiation, in part, by stimulating expression of the mitochondria-localized antioxidant enzyme manganese superoxide dismutase (MnSOD). Blocking RelB activation suppresses MnSOD expression and sensitizes prostate cancer cells to radiation. These results suggest that RelB-mediated modulation of the antioxidant capacity of prostate cancer cells is an important mechanism of radiation resistance. Therefore, targeting RelB activation may prove to be a valuable weapon in the oncologist's arsenal to defeat aggressive and radiation-resistant prostate cancer.
Holley
Aaron K
AK
Graduate Center for Toxicology, University of Kentucky, Lexington, Kentucky 40536, USA.
Xu
Yong
Y
St Clair
Daret K
DK
St Clair
William H
WH
D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy*; D011839:Radiation, Ionizing; D011878:Radiotherapy / Q000379:methods; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase / Q000378:metabolism*; D051841:Transcription Factor RelB / Q000502:physiology*
D000975:Antioxidants; D016328:NF-kappa B; C497593:RELB protein, human; D017382:Reactive Oxygen Species; D051841:Transcription Factor RelB; D013482:Superoxide Dismutase