title: Redox signalling to nuclear regulatory proteins by reactive oxygen species contributes to oestrogen-induced growth of breast cancer cells.
abstract: BACKGROUND
  17β-Oestradiol (E2)-induced reactive oxygen species (ROS) have been implicated in regulating the growth of breast cancer cells. However, the underlying mechanism of this is not clear. Here we show how ROS through a novel redox signalling pathway involving nuclear respiratory factor-1 (NRF-1) and p27 contribute to E2-induced growth of MCF-7 breast cancer cells.
  
  
  METHODS
  Chromatin immunoprecipitation, qPCR, mass spectrometry, redox western blot, colony formation, cell proliferation, ROS assay, and immunofluorescence microscopy were used to study the role of NRF-1.
  
  
  RESULTS
  The major novel finding of this study is the demonstration of oxidative modification of phosphatases PTEN and CDC25A by E2-generated ROS along with the subsequent activation of AKT and ERK pathways that culminated in the activation of NRF-1 leading to the upregulation of cell cycle genes. 17β-Oestradiol-induced ROS by influencing nuclear proteins p27 and Jab1 also contributed to the growth of MCF-7 cells.
  
  
  CONCLUSIONS
  Taken together, our results present evidence in the support of E2-induced ROS-mediated AKT signalling leading to the activation of NRF-1-regulated cell cycle genes as well as the impairment of p27 activity, which is presumably necessary for the growth of MCF-7 cells. These observations are important because they provide a new paradigm by which oestrogen may contribute to the growth of breast cancer.
authors.affiliation: Department of Environmental and Occupational Health, Florida International University, 11200 SW 8th Street, Miami, FL 33199-0001, USA.
authors.forename: V O
authors.initials: VO
authors.lastname: Okoh
authors.affiliation: Department of Environmental and Occupational Health, Florida International University, 11200 SW 8th Street, Miami, FL 33199-0001, USA.
authors.forename: N A
authors.initials: NA
authors.lastname: Garba
authors.affiliation: Department of Environmental and Occupational Health, University of Arkansas for Medical Sciences, Little Rock, AR 72204, USA.
authors.forename: R B
authors.initials: RB
authors.lastname: Penney
authors.affiliation: Department of Environmental and Occupational Health, Florida International University, 11200 SW 8th Street, Miami, FL 33199-0001, USA.
authors.forename: J
authors.initials: J
authors.lastname: Das
authors.affiliation: Department of Environmental and Occupational Health, Florida International University, 11200 SW 8th Street, Miami, FL 33199-0001, USA.
authors.forename: A
authors.initials: A
authors.lastname: Deoraj
authors.affiliation: Department of Environmental Toxicology, The Institute of Environmental and Human Health (TIEHH), Texas Tech University, Lubbock, TX 79409, USA.
authors.forename: K P
authors.initials: KP
authors.lastname: Singh
authors.affiliation: Department of Neuroscience and Cell Biology, UTMB, Galveston, TX 77555, USA.
authors.forename: S
authors.initials: S
authors.lastname: Sarkar
authors.affiliation: Department of Environmental and Occupational Health, Florida International University, 11200 SW 8th Street, Miami, FL 33199-0001, USA.
authors.forename: Q
authors.initials: Q
authors.lastname: Felty
authors.affiliation: Department of Biostatistics, Florida International University, Miami, FL 33199, USA.
authors.forename: C
authors.initials: C
authors.lastname: Yoo
authors.affiliation: Research Service, VA Medical Center, 1201 NW 16th Street, Miami, FL 33125, USA.
authors.forename: R M
authors.initials: RM
authors.lastname: Jackson
authors.affiliation: 1] Department of Environmental and Occupational Health, Florida International University, 11200 SW 8th Street, Miami, FL 33199-0001, USA [2] Research Service, VA Medical Center, 1201 NW 16th Street, Miami, FL 33125, USA.
authors.forename: D
authors.initials: D
authors.lastname: Roy
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics*; D004958:Estradiol / Q000235:genetics / Q000378:metabolism; D004967:Estrogens / Q000235:genetics / Q000378:metabolism*; D005260:Female; D018816:Genes, cdc / Q000235:genetics; D006801:Humans; D061986:MCF-7 Cells; D051266:Nuclear Respiratory Factor 1 / Q000235:genetics / Q000378:metabolism*; D010084:Oxidation-Reduction; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: D004967:Estrogens; C495633:NRF1 protein, human; D051266:Nuclear Respiratory Factor 1; D018809:Proliferating Cell Nuclear Antigen; D017382:Reactive Oxygen Species; C413374:p27 antigen; D004958:Estradiol; D051057:Proto-Oncogene Proteins c-akt