The oxidative stress in breast tumors of postmenopausal women is ER¦Á/ER¦Â ratio dependent

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• 作者：Jorge Sastre-Serra^a ; ¹ ; Mercedes Nadal-Serrano^a ; ¹ ; Daniel Gabriel Pons^a ; Adamo Valle^a ; Isabel Garau^b ; Magdalena Garcí ; a-Bonafé ; ^b ; Jordi Oliver^a ; Pilar Roca^a ; ^{pilar.roca@uib.es}
• 关键词：Breast tumor ; Estrogen receptor ¦Á ; Estrogen receptor ¦Â ; Receptor ratio ; Oxidative stress ; Free radicals
• 刊名：Free Radical Biology and Medicine
• 出版年：2013
• 出版时间：August, 2013
• 年：2013
• 卷：61
• 期：Complete
• 页码：11-17
• 全文大小：538 K

文摘

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, ER¦Á and ER¦Â, 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 ER¦Á/ER¦Â 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 ER¦Á/ER¦Â 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 ER¦Á were significantly and positively correlated with ER¦Á/ER¦Â ratio. However, carbonyl groups, catalase, CuZn-superoxide dismutase, UCP5, SIRT3, and ER¦Â were significantly and negatively correlated with ER¦Á/ER¦Â ratio. From the independent variables included in the step-by-step stepwise multiple linear regression analysis, only the ER¦Á/ER¦Â ratio was independently associated with carbonyl groups. Surprisingly, these low ER¦Á/ER¦Â 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.