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.
| Original language | English |
|---|---|
| Pages (from-to) | 436-450 |
| Number of pages | 15 |
| Journal | Free Radical Biology and Medicine |
| Volume | 99 |
| DOIs | |
| Publication status | Published - 1 Oct 2016 |
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Keywords
- Breast cancer cells
- Catalase
- Chromatin remodeling
- JunB
- Oxidative stress
- RARα
Cite this
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Chromatin remodeling regulates catalase expression during cancer cells adaptation to chronic oxidative stress. / Glorieux, Christophe; Sandoval, Juan Marcelo; Fattaccioli, Antoine; Dejeans, Nicolas; Garbe, James C.; Dieu, Marc; Verrax, Julien; Renard, Patricia; Huang, Peng; Calderon, Pedro Buc.
In: Free Radical Biology and Medicine, Vol. 99, 01.10.2016, p. 436-450.Research output: Contribution to journal › Article
TY - JOUR
T1 - Chromatin remodeling regulates catalase expression during cancer cells adaptation to chronic oxidative stress
AU - Glorieux, Christophe
AU - Sandoval, Juan Marcelo
AU - Fattaccioli, Antoine
AU - Dejeans, Nicolas
AU - Garbe, James C.
AU - Dieu, Marc
AU - Verrax, Julien
AU - Renard, Patricia
AU - Huang, Peng
AU - Calderon, Pedro Buc
PY - 2016/10/1
Y1 - 2016/10/1
N2 - 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.
AB - 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.
KW - Breast cancer cells
KW - Catalase
KW - Chromatin remodeling
KW - JunB
KW - Oxidative stress
KW - RARα
UR - http://www.scopus.com/inward/record.url?scp=84986267414&partnerID=8YFLogxK
U2 - 10.1016/j.freeradbiomed.2016.08.031
DO - 10.1016/j.freeradbiomed.2016.08.031
M3 - Article
AN - SCOPUS:84986267414
VL - 99
SP - 436
EP - 450
JO - Free Radicals in Biology and Medicine
JF - Free Radicals in Biology and Medicine
SN - 0891-5849
ER -