title: The ERalpha/ERbeta ratio determines oxidative stress in breast cancer cell lines in response to 17beta-estradiol.
abstract: The effects of 17beta-estradiol (E2) are mediated through activation of estrogen receptors (ER): ERalpha and ERbeta. It is known that ERalpha/ERbeta ratio is higher in breast tumors than in normal tissue. Since antioxidant enzymes and uncoupling proteins (UCPs) are reactive oxygen species (ROS) production and mitochondrial biogenesis regulators, our aim was to study the E2-effect on oxidative stress, antioxidant enzyme expression, and UCPs in breast cancer cell lines with different ERalpha/ERbeta ratios. The lower ERalpha/ERbeta ratio T47D cell line showed low ROS production and high UCP5 levels. However, the higher ERalpha/ERbeta ratio MCF-7 cell line showed an up-regulation of antioxidant enzymes and UCPs, yet exhibited high oxidative stress. As a result, a decrease in antioxidant enzyme activities and UCP2 protein levels, coupled with an increase in oxidative damage was found. On the whole, these results show different E2-effects on oxidative stress regulation, modulating UCPs, and antioxidant enzymes, which were ERalpha/ERbeta ratio dependent in breast cancer cell lines.
authors.affiliation: Grupo multidisciplinar de Oncología Traslacional, Institut Universitari d'Investigació en Ciències de la Salut (IUNICS), Palma de Mallorca, Illes Balears, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Nadal-Serrano
authors.forename: Jorge
authors.initials: J
authors.lastname: Sastre-Serra
authors.forename: Daniel Gabriel
authors.initials: DG
authors.lastname: Pons
authors.forename: Antonia María
authors.initials: AM
authors.lastname: Miró
authors.forename: Jordi
authors.initials: J
authors.lastname: Oliver
authors.forename: Pilar
authors.initials: P
authors.lastname: Roca
mesh_terms: D000975:Antioxidants / Q000378:metabolism; D002374:Catalase / Q000032:analysis / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D004789:Enzyme Activation; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D061986:MCF-7 Cells; D053078:Membrane Potential, Mitochondrial; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D063269:Mitochondrial Turnover; D000071245:Mitochondrial Uncoupling Proteins; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D000071246:Uncoupling Protein 2
chemical_list: D000975:Antioxidants; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D007473:Ion Channels; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D000071245:Mitochondrial Uncoupling Proteins; D009419:Nerve Tissue Proteins; D017382:Reactive Oxygen Species; C116584:SLC25A14 protein, human; C000604389:UCP2 protein, human; D000071246:Uncoupling Protein 2; D004958:Estradiol; D002374:Catalase; D013482:Superoxide Dismutase