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

dc.authoridkarakas, bahriye/0000-0001-9616-4656|KUTUK, OZGUR/0000-0001-9854-7220|AKA, YELİZ/0000-0002-1708-4779|Temel, Sehime G/0000-0002-9802-0880
dc.authorwosidkarakas, bahriye/GOK-0965-2022
dc.authorwosidKarakas, Bahriye/GOP-0970-2022
dc.authorwosidKUTUK, OZGUR/AAH-1671-2019
dc.authorwosidGul, Ozgur/A-7841-2011
dc.authorwosidAKA, YELİZ/JXM-3830-2024
dc.contributor.authorKarakas, Bahriye
dc.contributor.authorAka, Yeliz
dc.contributor.authorGiray, Asli
dc.contributor.authorTemel, Sehime Gulsun
dc.contributor.authorAcikbas, Ufuk
dc.contributor.authorBasaga, Huveyda
dc.contributor.authorGul, Ozgur
dc.date.accessioned2024-07-18T20:56:57Z
dc.date.available2024-07-18T20:56:57Z
dc.date.issued2021
dc.departmentİstanbul Bilgi Üniversitesien_US
dc.description.abstractBreast cancer is the most common cancer with a high rate of mortality and morbidity among women worldwide. Estrogen receptor status is an important prognostic factor and endocrine therapy is the choice of first-line treatment in ER-positive breast cancer. However, most tumors develop resistance to endocrine therapy. Here we demonstrate that BH3 profiling technology, in particular, dynamic BH3 profiling can predict the response to endocrine therapy agents as well as the development of acquired resistance in breast cancer cells independent of estrogen receptor status. Immunofluorescence analysis and subcellular fractionation experiments revealed distinct ER-alpha and ER-beta subcellular localization patterns in breast cancer cells, including mitochondrial localization of both receptor subtypes. shRNA-mediated depletion of ER-beta in breast cancer cells led to resistance to endocrine therapy agents and selective reconstitution of ER-beta in mitochondria restored sensitivity. Notably, mitochondria-targeted ER-alpha did not restore sensitivity, even conferred further resistance to endocrine therapy agents. In addition, expressing mitochondria-targeted ER-beta in breast cancer cells resulted in decreased mitochondrial respiration alongside increased total ROS and mitochondrial superoxide production. Furthermore, our data demonstrated that mitochondrial ER-beta can be successfully targeted by the selective ER-beta agonist Erteberel. Thus, our findings provide novel findings on mitochondrial estrogen signaling in breast cancer cells and suggest the implementation of the dynamic BH3 technique as a tool to predict acquired endocrine therapy resistance.en_US
dc.description.sponsorshipTUBITAK [113S872]; Science Academy BAGEP programen_US
dc.description.sponsorshipWe thank Prof. Myles Brown who kindly provides ER-alpha and ER-beta expression plasmids. This work was supported by TUBITAK (Project no: 113S872). Ozgur Kutuk acknowledges support from the Science Academy BAGEP program.en_US
dc.identifier.doi10.1038/s41420-021-00573-2
dc.identifier.issn2058-7716
dc.identifier.issue1en_US
dc.identifier.pmid34294688en_US
dc.identifier.scopus2-s2.0-85111109695en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.urihttps://doi.org/10.1038/s41420-021-00573-2
dc.identifier.urihttps://hdl.handle.net/11411/8924
dc.identifier.volume7en_US
dc.identifier.wosWOS:000678973900001en_US
dc.identifier.wosqualityQ2en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherSpringernatureen_US
dc.relation.ispartofCell Death Discoveryen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectEr-Alphaen_US
dc.subjectBetaen_US
dc.subjectExpressionen_US
dc.subjectGrowthen_US
dc.subjectLocalizationen_US
dc.subjectResistanceen_US
dc.titleMitochondrial estrogen receptors alter mitochondrial priming and response to endocrine therapy in breast cancer cellsen_US
dc.typeArticleen_US

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