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

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datacite.alternateIdentifier.citationFRONTIERS IN ENDOCRINOLOGY,Vol.11,,2020
datacite.alternateIdentifier.doi10.3389/fendo.2020.563165
datacite.creatorMolina, Luis
datacite.creatorBustamante, Felipe
datacite.creatorOrtloff Trautmann, Alexander
datacite.creatorRamos, Iraidi
datacite.creatorEhrenfeld, Pamela
datacite.creatorFigueroa, Carlos D.
datacite.date2020
datacite.subject.englishGPER-1
datacite.subject.englishGPR30
datacite.subject.englishG1 agonist
datacite.subject.englishcalcium signaling
datacite.subject.englishtamoxifen resistance
datacite.subject.englishkinin B1 receptor
datacite.subject.englishbreast cancer
datacite.subject.englishcell proliferation
datacite.titleContinuous Exposure of Breast Cancer Cells to Tamoxifen Upregulates GPER-1 and Increases Cell Proliferation
dc.date.accessioned2021-04-30T16:47:00Z
dc.date.available2021-04-30T16:47:00Z
dc.description.abstractGPER-1 is a novel membrane sited G protein-coupled estrogen receptor. Clinical studies have shown that patients suffering an estrogen receptor alpha (ER alpha)/GPER-1 positive, breast cancer have a lower survival rate than those who have developed ER alpha-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 alpha-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+]imobilization, a key signaling pathway. Breast cancer cells continuously treated with tamoxifen, exhibited a robust [Ca2+]imobilization 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+]imobilization 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 alpha 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 obtainedin vitroto the patients, our results shed some light on the occurrence of drug resistance in breast cancer patients who are ER alpha/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.
dc.identifier.urihttp://repositoriodigital.uct.cl/handle/10925/3481
dc.language.isoen
dc.publisherFRONTIERS MEDIA SA
dc.sourceFRONTIERS IN ENDOCRINOLOGY
oaire.resourceTypeArticle
uct.catalogadorWOS
uct.indizacionSCI
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