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Chromatin remodeling regulates catalase expression during cancer cells adaptation to chronic oxidative stress
- Source :
- Free Radicals in Biology and Medicine. 99:436-450
- Publication Year :
- 2016
- Publisher :
- Elsevier, 2016.
-
Abstract
- Regulation of ROS metabolism plays a major role in cellular adaptation to oxidative stress in cancer cells, but the molecular mechanism that regulates catalase, a key antioxidant enzyme responsible for conversion of hydrogen peroxide to water and oxygen, remains to be elucidated. Therefore, we investigated the transcriptional regulatory mechanism controlling catalase expression in three human mammary cell lines: the normal mammary epithelial 250MK primary cells, the breast adenocarcinoma MCF-7 cells and an experimental model of MCF-7 cells resistant against oxidative stress resulting from chronic exposure to H2O2 (Resox), in which catalase was overexpressed. Here we identify a novel promoter region responsible for the regulation of catalase expression at −1518/−1226 locus and the key molecules that interact with this promoter and affect catalase transcription. We show that the AP-1 family member JunB and retinoic acid receptor alpha (RARα) mediate catalase transcriptional activation and repression, respectively, by controlling chromatin remodeling through a histone deacetylases-dependent mechanism. This regulatory mechanism plays an important role in redox adaptation to chronic exposure to H2O2 in breast cancer cells. Our study suggests that cancer adaptation to oxidative stress may be regulated by transcriptional factors through chromatin remodeling, and reveals a potential new mechanism to target cancer cells.
- Subjects :
- 0301 basic medicine
Transcription, Genetic
Cellular adaptation
JUNB
medicine.disease_cause
Biochemistry
Histone Deacetylases
Chromatin remodeling
Cell Line
03 medical and health sciences
Cell Line, Tumor
Physiology (medical)
medicine
Humans
Promoter Regions, Genetic
Transcription factor
Breast cancer cells
Base Sequence
biology
Retinoic Acid Receptor alpha
Epithelial Cells
Hydrogen Peroxide
Chromatin Assembly and Disassembly
Catalase
Adaptation, Physiological
Chromatin
RARα
Gene Expression Regulation, Neoplastic
030104 developmental biology
Retinoic acid receptor alpha
Oxidative stress
Cancer cell
MCF-7 Cells
biology.protein
Cancer research
Reactive Oxygen Species
JunB
Signal Transduction
Transcription Factors
Subjects
Details
- Language :
- English
- ISSN :
- 08915849
- Volume :
- 99
- Database :
- OpenAIRE
- Journal :
- Free Radicals in Biology and Medicine
- Accession number :
- edsair.doi.dedup.....bf79769e15027ef69d4f19842542fdf6