The glucocorticoid receptor interferes with progesterone receptor-dependent genomic regulation in breast cancer cells

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  • dc.contributor.author Ogara, Maria F.
  • dc.contributor.author Rodríguez Seguí, Santiago A.
  • dc.contributor.author Marini, Melisa
  • dc.contributor.author Silvina Nacht, Ana
  • dc.contributor.author Stortz, Martin
  • dc.contributor.author Levi, Valeria
  • dc.contributor.author Presman, Diego M.
  • dc.contributor.author Vicent, Guillermo Pablo
  • dc.contributor.author Pecci, Adali
  • dc.date.accessioned 2020-04-06T10:06:38Z
  • dc.date.available 2020-04-06T10:06:38Z
  • dc.date.issued 2019
  • dc.description.abstract The glucocorticoid and progesterone receptors (GR and PR) are closely related members of the steroid receptor family. Despite sharing similar structural and functional characteristics; the cognate hormones display very distinct physiological responses. In mammary epithelial cells, PR activation is associated with the incidence and progression of breast cancer, whereas the GR is related to growth suppression and differentiation. Despite their pharmacological relevance, only a few studies have compared GR and PR activities in the same system. Using a PR+/GR+ breast cancer cell line, here we report that either glucocorticoid-free or dexamethasone (DEX)-activated GR inhibits progestin-dependent gene expression associated to epithelial-mesenchymal-transition and cell proliferation. When both receptors are activated with their cognate hormones, PR and GR can form part of the same complex according to co-immunoprecipitation, quantitative microscopy and sequential ChIP experiments. Moreover, genome-wide studies in cells treated with either DEX or R5020, revealed the presence of several regions co-bound by both receptors. Surprisingly, GR also binds novel genomic sites in cells treated with R5020 alone. This progestin-induced GR binding was enriched in REL DNA motifs and located close to genes coding for chromatin remodelers. Understanding GR behavior in the context of progestin-dependent breast cancer could provide new targets for tumor therapy.
  • dc.description.sponsorship Spanish Ministry of Economy and Competitiveness, Spain [SAF2016-75006P]; CONICET [PIP112-200801-00859]; Agencia Nacional de Programación Científica y Tecnológica [Préstamo BID-PICT2014-0630]; University of Buenos Aires, Argentina [20820180100745BA]. CONICET-Argentina (M.F.O., S.A.R.S., V.L, D.M.P, A.P.); Spanish National Research Council (CSIC), Spain (to G.P.V.); IUBMB Short-term Scholarship (to M.F.O, M.S.M.); EMBO Short-term Scholarship (to M.F.O.).
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Ogara MF, Rodríguez-Seguí SA, Marini M, Nacht AS, Stortz M, Levi V, Presman DM, Vicent GP, Pecci A. The glucocorticoid receptor interferes with progesterone receptor-dependent genomic regulation in breast cancer cells. Nucleic Acids Res. 2019; 47(20):10645-61. DOI: 10.1093/nar/gkz857
  • dc.identifier.doi http://dx.doi.org/10.1093/nar/gkz857
  • dc.identifier.issn 0305-1048
  • dc.identifier.uri http://hdl.handle.net/10230/44161
  • dc.language.iso eng
  • dc.publisher Oxford University Press
  • dc.relation.ispartof Nucleic Acids Res. 2019; 47(20):10645-61
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2016-75006P
  • dc.rights © The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by-nc/4.0/
  • dc.subject.keyword Gene regulation
  • dc.subject.keyword Chromatin and epigenetics
  • dc.title The glucocorticoid receptor interferes with progesterone receptor-dependent genomic regulation in breast cancer cells
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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Articles (Center for Genomic Regulation (CRG))
Articles (Departament de Medicina i Ciències de la Vida)