Continuous Exposure of Breast Cancer Cells to Tamoxifen Upregulates GPER-1 and Increases Cell Proliferation

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datacite.alternateIdentifier.citationFrontiers in Endocrinology, 11, 2020
datacite.alternateIdentifier.doi10.3389/fendo.2020.563165
datacite.alternateIdentifier.issn1664-2392
datacite.creatorMolina, Luis
datacite.creatorBustamante, Felipe A.
datacite.creatorOrtloff, Alexander R.
datacite.creatorRamos, Iraidi
datacite.creatorEhrenfeld, Pamela
datacite.creatorFigueroa, Carlos D.
datacite.date2020
datacite.rightsAcceso abierto
datacite.subjectBreast Cancer
datacite.subjectCalcium Signaling
datacite.subjectCell Proliferation
datacite.subjectG1 Agonist
datacite.subjectGper-1, Gpr30
datacite.subjectKinin B1 Receptor
datacite.subjectTamoxifen Resistance
datacite.subjectDimethyl Sulfoxide
datacite.subjectLeupeptin
datacite.subjectPeroxidase
datacite.subjectTamoxifen
datacite.subjectBuffer
datacite.subjectCalcium Chelating Agent
datacite.subjectDimethyl Sulfoxide
datacite.subjectG Protein Coupled Receptor 30
datacite.subjectKinin
datacite.subjectKinin B1 Receptor
datacite.subjectLeupeptin
datacite.subjectPeroxidase
datacite.subjectTamoxifen
datacite.subjectUnclassified Drug
datacite.subjectArticle
datacite.subjectBreast Cancer
datacite.subjectBreast Cancer Cell Line
datacite.subjectBreast Tumor
datacite.subjectCalcium Mobilization
datacite.subjectCancer Growth
datacite.subjectCancer Patient
datacite.subjectCell Proliferation
datacite.subjectCell Proliferation Assay
datacite.subjectControlled Study
datacite.subjectFemale
datacite.subjectGene
datacite.subjectGene Expression
datacite.subjectGene Overexpression
datacite.subjectGper 1 Gene
datacite.subjectHuman
datacite.subjectHuman Cell
datacite.subjectImmunodetection
datacite.subjectIn Vitro Study
datacite.subjectMcf-7 Cell Line
datacite.subjectMobilization
datacite.subjectPolyacrylamide Gel Electrophoresis
datacite.subjectUpregulation
datacite.subjectWestern Blotting
datacite.titleContinuous Exposure of Breast Cancer Cells to Tamoxifen Upregulates GPER-1 and Increases Cell Proliferation
dc.contributor.authorORTLOFF TRAUTMANN, ALEXANDER
dc.description.abstractGPER-1 is a novel membrane sited G protein-coupled estrogen receptor. Clinical studies have shown that patients suffering an estrogen receptor ? (ER?)/GPER-1 positive, breast cancer have a lower survival rate than those who have developed ER?-positive/GPER-1 negative tumors. Moreover, absence of GPER-1 improves the prognosis of patients treated with tamoxifen, the most used selective estrogen receptor modulator to treat ER?-positive breast cancer. MCF-7 breast cancer cells were continuously treated with 1,000 nM tamoxifen for 7 days to investigate its effect on GPER-1 protein expression, cell proliferation and intracellular [Ca2+]i mobilization, a key signaling pathway. Breast cancer cells continuously treated with tamoxifen, exhibited a robust [Ca2+]i mobilization after stimulation with 1,000 nM tamoxifen, a response that was blunted by preincubation of cells with G15, a commercial GPER-1 antagonist. Continuously treated cells also displayed a high [Ca2+]i mobilization in response to a commercial GPER-1 agonist (G1) and to estrogen, in a magnitude that doubled the response observed in untreated cells and was almost completely abolished by G15. Proliferation of cells continuously treated with tamoxifen and stimulated with 2,000 nM tamoxifen, was also higher than that observed in untreated cells in a degree that was approximately 90% attributable to GPER-1. Finally, prolonged tamoxifen treatment did not increase ER? expression, but did overexpress the kinin B1 receptor, another GPCR, which we have previously shown is highly expressed in breast tumors and increases proliferation of breast cancer cells. Although we cannot fully extrapolate the results obtained in vitro to the patients, our results shed some light on the occurrence of drug resistance in breast cancer patients who are ER?/GPER-1 positive, have been treated with tamoxifen and display low survival rate. Overexpression of kinin B1 receptor may explain the increased proliferative response observed in breast tumors under continuous treatment with tamoxifen. © 2020 Elsevier B.V., All rights reserved.
dc.description.ia_keywordgper, tamoxifen, breast, cells, cancer, treated, receptor
dc.formatPDF
dc.identifier.urihttps://repositoriodigital.uct.cl/handle/10925/3481
dc.language.isoen
dc.publisherFrontiers Media
dc.relationinstname: ANID
dc.relationreponame: Repositorio Digital RI2.0
dc.rights.driverinfo:eu-repo/semantics/openAccess
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/cl/
dc.sourceFrontiers in Endocrinology
dc.subject.ia_oecd1nCiencias Naturales
dc.subject.ia_oecd2nCiencias Biológicas
dc.subject.ia_oecd3nBiología General
dc.type.driverinfo:eu-repo/semantics/article
dc.type.driverhttp://purl.org/coar/resource_type/c_2df8fbb1
dc.type.openaireinfo:eu-repo/semantics/publishedVersion
dspace.entity.typePublication
oaire.citationEdition2020
oaire.citationTitleFrontiers in Endocrinology
oaire.citationVolume11
oaire.fundingReferenceANID FONDECYT 1201635 (Regular)
oaire.fundingReferenceUniversidad Austral de Chile Vicerrectoría de Investigación
oaire.fundingReferenceUniversidad San Sebastián Facultad de Medicina y Ciencia
oaire.licenseConditionObra bajo licencia Creative Commons Atribución 4.0 Internacional
oaire.licenseCondition.urihttps://creativecommons.org/licenses/by/4.0/
oaire.resourceTypeArtículo
oaire.resourceType.enArticle
relation.isAuthorOfPublication798755f1-1bb9-449a-b2e2-d4bbe38ca016
relation.isAuthorOfPublication.latestForDiscovery798755f1-1bb9-449a-b2e2-d4bbe38ca016
uct.catalogadorjvu
uct.comunidadRecursos Naturalesen_US
uct.departamentoDepartamento de Ciencias Veterinarias y Salud Pública
uct.facultadFacultad de Recursos Naturales
uct.indizacionScience Citation Index Expanded - SCIE
uct.indizacionSCOPUS
uct.indizacionWOS
uct.indizacionDOAJ
uct.indizacionPubMed
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