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C/EBPα mediates the growth inhibitory effect of progestins on breast cancer cells

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dc.contributor.author Nacht, A. Silvina
dc.contributor.author Ferrari, Roberto
dc.contributor.author Zaurín Quer, Roser
dc.contributor.author Scabia, Valentina
dc.contributor.author Carbonell-Caballero, Jose
dc.contributor.author Le Dily, François
dc.contributor.author Quilez Oliete, Javier
dc.contributor.author Leopoldi, Alexandra
dc.contributor.author Brisken, Cathrin
dc.contributor.author Beato, Miguel
dc.contributor.author Vicent, Guillermo Pablo
dc.date.accessioned 2020-02-10T12:00:46Z
dc.date.available 2020-02-10T12:00:46Z
dc.date.issued 2019
dc.identifier.citation Nacht, A S, Ferrari R, Zaurin R, Sacabia V, Carbonell-Caballero J, Le Dily F et al. C/EBPα mediates the growth inhibitory effect of progestins on breast cancer cells. EMBO J. 2019;38(18):e101426. DOI: 10.15252/embj.2018101426
dc.identifier.issn 0261-4189
dc.identifier.uri http://hdl.handle.net/10230/43543
dc.description.abstract Steroid hormones are key gene regulators in breast cancer cells. While estrogens stimulate cell proliferation, progestins activate a single cell cycle followed by proliferation arrest. Here, we use biochemical and genome-wide approaches to show that progestins achieve this effect via a functional crosstalk with C/EBPα. Using ChIP-seq, we identify around 1,000 sites where C/EBPα binding precedes and helps binding of progesterone receptor (PR) in response to hormone. These regions exhibit epigenetic marks of active enhancers, and C/EBPα maintains an open chromatin conformation that facilitates loading of ligand-activated PR. Prior to hormone exposure, C/EBPα favors promoter-enhancer contacts that assure hormonal regulation of key genes involved in cell proliferation by facilitating binding of RAD21, YY1, and the Mediator complex. Knockdown of C/EBPα disrupts enhancer-promoter contacts and decreases the presence of these architectural proteins, highlighting its key role in 3D chromatin looping. Thus, C/EBPα fulfills a previously unknown function as a potential growth modulator in hormone-dependent breast cancer.
dc.description.sponsorship The experimental work was supported by grants from the Departament d’Innovació, Universitat i Empresa (DIUiE), and the Spanish Ministry of Economy and Competitiveness (SAF2016-75006P), “Centro de Excelencia Severo Ochoa 2013-2017”, SEV-2012-0208 and ERC Synergy Grant “4DGenome” nr: 609989
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher EMBO Press
dc.relation.ispartof EMBO Journal. 2019;38(18):e101426
dc.relation.isreferencedby https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE132649
dc.subject.other Mama -- Càncer
dc.subject.other Progesterona
dc.subject.other Proteïnes
dc.title C/EBPα mediates the growth inhibitory effect of progestins on breast cancer cells
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.15252/embj.2018101426
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2016-75006P
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/609989
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/acceptedVersion


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