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RelB regulates manganese superoxide dismutase gene and resistance to ionizing radiation of prostate cancer cells
Author(s) -
Holley Aaron K.,
Xu Yong,
Clair Daret K. St.,
Clair William H. St.
Publication year - 2010
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2010.05613.x
Subject(s) - relb , prostate cancer , cancer research , cancer , superoxide dismutase , radioresistance , cancer cell , medicine , ionizing radiation , radiation therapy , chemistry , oxidative stress , nfkb1 , biochemistry , gene , transcription factor , irradiation , physics , nuclear physics
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‐κB 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‐κB 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.