Journal article
Nuclear Factor-κB and Manganese Superoxide Dismutase Mediate Adaptive Radioresistance in Low-Dose Irradiated Mouse Skin Epithelial Cells
Cancer research (Chicago, Ill.), Vol.67(7), pp.3220-3228
04/01/2007
DOI: 10.1158/0008-5472.CAN-06-2728
PMID: 17409430
Abstract
Mechanisms governing inducible resistance to ionizing radiation in untransformed epithelial cells pre-exposed to low-dose ionizing radiation (LDIR; ≤10 cGy) are not well understood. The present study provides evidence that pre-exposure to 10 cGy X-rays increases clonogenic survival of mouse skin JB6P+ epithelial cells subsequently exposed to 2 Gy doses of γ-rays. To elucidate the molecular pathways of LDIR-induced adaptive radioresistance, the transcription factor nuclear factor-κB (NF-κB) and a group of NF-κB–related proteins [i.e., p65, manganese superoxide dismutase (MnSOD), phosphorylated extracellular signal-regulated kinase, cyclin B1, and 14-3-3ζ] were identified to be activated as early as 15 min after LDIR. Further analysis revealed that a substantial amount of both 14-3-3ζ and cyclin B1 accumulated in the cytoplasm at 4 to 8 h when cell survival was enhanced. The nuclear 14-3-3ζ and cyclin B1 were reduced and increased at 4 and 24 h, respectively, after LDIR. Using YFP-fusion gene expression vectors, interaction between 14-3-3ζ and cyclin B1 was visualized in living cells, and LDIR enhanced the nuclear translocation of the 14-3-3ζ/cyclin B1 complex. Treatment of JB6P+ cells with the NF-κB inhibitor IMD-0354 suppressed LDIR-induced expression of MnSOD, 14-3-3ζ, and cyclin B1 and diminished the adaptive radioresistance. In addition, treatment with small interfering RNA against mouse MnSOD was shown to inhibit the development of LDIR-induced radioresistance. Together, these results show that NF-κB, MnSOD, 14-3-3ζ, and cyclin B1 contribute to LDIR-induced adaptive radioresistance in mouse skin epithelial cells. [Cancer Res 2007;67(7):3220–8]
Details
- Title: Subtitle
- Nuclear Factor-κB and Manganese Superoxide Dismutase Mediate Adaptive Radioresistance in Low-Dose Irradiated Mouse Skin Epithelial Cells
- Creators
- Ming FanKazi Mokim AhmedMitchell C ColemanDouglas R SpitzJian Jian Li
- Resource Type
- Journal article
- Publication Details
- Cancer research (Chicago, Ill.), Vol.67(7), pp.3220-3228
- DOI
- 10.1158/0008-5472.CAN-06-2728
- PMID
- 17409430
- NLM abbreviation
- Cancer Res
- ISSN
- 0008-5472
- eISSN
- 1538-7445
- Language
- English
- Date published
- 04/01/2007
- Academic Unit
- Pathology; Orthopedics and Rehabilitation; Radiation Oncology
- Record Identifier
- 9984040014202771
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