Chromatin remodeling regulates catalase expression during cancer cells adaptation to chronic oxidative stress

Christophe Glorieux, Juan Marcelo Sandoval, Antoine Fattaccioli, Nicolas Dejeans, James C. Garbe, Marc Dieu, Julien Verrax, Patricia Renard, Peng Huang, Pedro Buc Calderon

Research output: Contribution to journalArticlepeer-review

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 languageEnglish
Pages (from-to)436-450
Number of pages15
JournalFree Radical Biology and Medicine
Volume99
DOIs
Publication statusPublished - 1 Oct 2016

Keywords

  • Breast cancer cells
  • Catalase
  • Chromatin remodeling
  • JunB
  • Oxidative stress
  • RARα

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