Mitochondrial estrogen receptors alter mitochondrial priming and response to endocrine therapy in breast cancer cells

Abstract Breast cancer is the most common with a high rate of mortality and morbidity among women worldwide. Estrogen receptor status an important prognostic factor endocrine therapy choice first-line treatment in ER-positive breast cancer. However, tumors develop resistance to therapy. Here we demonstrate that BH3 profiling technology, particular, dynamic can predict response agents as well development acquired cells independent estrogen status. Immunofluorescence analysis subcellular fractionation experiments revealed distinct ER-α ER-β localization patterns cells, including mitochondrial both subtypes. shRNA-mediated depletion led selective reconstitution mitochondria restored sensitivity. Notably, mitochondria-targeted did not restore sensitivity, even conferred further agents. In addition, expressing resulted decreased respiration alongside increased total ROS superoxide production. Furthermore, our data demonstrated be successfully targeted by agonist Erteberel. Thus, findings provide novel on signaling suggest implementation technique tool resistance.