title: Chromatin remodeling regulates catalase expression during cancer cells adaptation to chronic oxidative stress.
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 H2O2in 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.
authors: Université catholique de Louvain, Louvain Drug Research Institute, Toxicology and Cancer Biology Research Group, 1200 Brussels, Belgium; Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, 510275 Guangzhou, China. Electronic address: christophe@sysucc.org.cn.
authors: Christophe
authors: C
authors: Glorieux
authors: Université catholique de Louvain, Louvain Drug Research Institute, Toxicology and Cancer Biology Research Group, 1200 Brussels, Belgium; Facultad de Ciencias de la Salud, Universidad Arturo Prat, 1100000 Iquique, Chile.
authors: Juan Marcelo
authors: JM
authors: Sandoval
authors: Laboratory of Biochemistry and Cell Biology (URBC), NAmur Research Institute for LIfe Sciences (NARILIS), University of Namur, 5000 Namur, Belgium.
authors: Antoine
authors: A
authors: Fattaccioli
authors: Université catholique de Louvain, Louvain Drug Research Institute, Toxicology and Cancer Biology Research Group, 1200 Brussels, Belgium.
authors: Nicolas
authors: N
authors: Dejeans
authors: Biological Systems and Engineering, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
authors: James C
authors: JC
authors: Garbe
authors: Mass Spectrometry University of Namur (MaSUN), University of Namur, 5000 Namur, Belgium.
authors: Marc
authors: M
authors: Dieu
authors: Université catholique de Louvain, Louvain Drug Research Institute, Toxicology and Cancer Biology Research Group, 1200 Brussels, Belgium.
authors: Julien
authors: J
authors: Verrax
authors: Laboratory of Biochemistry and Cell Biology (URBC), NAmur Research Institute for LIfe Sciences (NARILIS), University of Namur, 5000 Namur, Belgium.
authors: Patricia
authors: P
authors: Renard
authors: Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, 510275 Guangzhou, China; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors: Peng
authors: P
authors: Huang
authors: Université catholique de Louvain, Louvain Drug Research Institute, Toxicology and Cancer Biology Research Group, 1200 Brussels, Belgium; Facultad de Ciencias de la Salud, Universidad Arturo Prat, 1100000 Iquique, Chile. Electronic address: pedro.buccalderon@uclouvain.be.
authors: Pedro Buc
authors: PB
authors: Calderon
mesh_terms: D000222:Adaptation, Physiological; D001483:Base Sequence; D002374:Catalase / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D002843:Chromatin / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology; D061986:MCF-7 Cells; D018384:Oxidative Stress; D011401:Promoter Regions, Genetic; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D000072482:Retinoic Acid Receptor alpha / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; C581727:JunB protein, human; C000607071:RARA protein, human; D017382:Reactive Oxygen Species; D000072482:Retinoic Acid Receptor alpha; D014157:Transcription Factors; D006861:Hydrogen Peroxide; D002374:Catalase; D006655:Histone Deacetylases
keywords: Breast cancer cells; Catalase; Chromatin remodeling; JunB; Oxidative stress; RARα