title: The oxidative stress in breast tumors of postmenopausal women is ERα/ERβ ratio dependent.
abstract: Estrogen receptor status is a diagnostic parameter in breast cancer treatment. Estrogen receptor presence is related to a better prognosis because the principal treatments attacking breast cancer tumors have their action site directed at the estrogen receptor. However, the two different subtypes of estrogen receptor, ERα and ERβ, have different functions. In this work an alternative point of view focusing on oxidative stress is shown, given that estrogen receptors regulate several proteins related to this oxidative stress, such as antioxidant enzymes, sirtuins, and uncoupling proteins. Postmenopausal human breast tumors with different ERα/ERβ ratios were analyzed to characterize the amount of oxidative stress, mitochondrial function, and proliferation-related and oxidative stress-activated signaling pathways. Results showed that tumors with a low ERα/ERβ ratio have greater oxidative damage and higher antioxidant enzyme protein levels, as well as uncoupling protein (UCP) and sirtuin 3 (SIRT3), and have high studied signaling pathway activation. Glutathione peroxidase, Complex V, Complex III, Complex II, Complex IV, AKT, SAPK, and ERα were significantly and positively correlated with ERα/ERβ ratio. However, carbonyl groups, catalase, CuZn-superoxide dismutase, UCP5, SIRT3, and ERβ were significantly and negatively correlated with ERα/ERβ ratio. From the independent variables included in the step-by-step stepwise multiple linear regression analysis, only the ERα/ERβ ratio was independently associated with carbonyl groups. Surprisingly, these low ERα/ERβ ratio tumors have poor prognosis for the patient, and these results and those of other authors suggest that these tumors are adapted to conditions of increased oxidative stress.
authors.affiliation: Grupo Multidisciplinar de Oncología Traslacional, Institut Universitari d'Investigació en Ciències de la Salut, Universitat de les Illes Balears, E07122 Palma de Mallorca, Illes Balears, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: Sastre-Serra
authors.affiliation: Grupo Multidisciplinar de Oncología Traslacional, Institut Universitari d'Investigació en Ciències de la Salut, Universitat de les Illes Balears, E07122 Palma de Mallorca, Illes Balears, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Nadal-Serrano
authors.affiliation: Grupo Multidisciplinar de Oncología Traslacional, Institut Universitari d'Investigació en Ciències de la Salut, Universitat de les Illes Balears, E07122 Palma de Mallorca, Illes Balears, Spain.
authors.forename: Daniel Gabriel
authors.initials: DG
authors.lastname: Pons
authors.affiliation: Grupo Multidisciplinar de Oncología Traslacional, Institut Universitari d'Investigació en Ciències de la Salut, Universitat de les Illes Balears, E07122 Palma de Mallorca, Illes Balears, Spain.
authors.forename: Adamo
authors.initials: A
authors.lastname: Valle
authors.affiliation: Grupo Multidisciplinar de Oncología Traslacional, Institut Universitari d'Investigació en Ciències de la Salut, Hospital Son Llàtzer, E07198 Palma de Mallorca, Illes Balears, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Garau
authors.affiliation: Grupo Multidisciplinar de Oncología Traslacional, Institut Universitari d'Investigació en Ciències de la Salut, Hospital Son Llàtzer, E07198 Palma de Mallorca, Illes Balears, Spain.
authors.forename: Magdalena
authors.initials: M
authors.lastname: García-Bonafé
authors.affiliation: Grupo Multidisciplinar de Oncología Traslacional, Institut Universitari d'Investigació en Ciències de la Salut, Universitat de les Illes Balears, E07122 Palma de Mallorca, Illes Balears, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Oliver
authors.affiliation: Grupo Multidisciplinar de Oncología Traslacional, Institut Universitari d'Investigació en Ciències de la Salut, Universitat de les Illes Balears, E07122 Palma de Mallorca, Illes Balears, Spain. Electronic address: pilar.roca@uib.es.
authors.forename: Pilar
authors.initials: P
authors.lastname: Roca
mesh_terms: D000368:Aged; D001943:Breast Neoplasms / Q000378:metabolism*; D047628:Estrogen Receptor alpha / Q000032:analysis / Q000502:physiology*; D047629:Estrogen Receptor beta / Q000032:analysis / Q000502:physiology*; D005260:Female; D006801:Humans; D007473:Ion Channels / Q000502:physiology; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000502:physiology; D018384:Oxidative Stress; D017698:Postmenopause; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D056566:Sirtuin 3 / Q000502:physiology; D000071256:Uncoupling Protein 1
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D007473:Ion Channels; D024101:Mitochondrial Proteins; D000071256:Uncoupling Protein 1; D051057:Proto-Oncogene Proteins c-akt; C466093:SIRT3 protein, human; D056566:Sirtuin 3
keywords: Breast tumor; Estrogen receptor α; Estrogen receptor β; Free radicals; Oxidative stress; Receptor ratio