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C/EBPα mediates the growth inhibitory effect of progestins on breast cancer cells.
Nacht, A Silvina; Ferrari, Roberto; Zaurin, Roser; Scabia, Valentina; Carbonell-Caballero, José; Le Dily, Francois; Quilez, Javier; Leopoldi, Alexandra; Brisken, Cathrin; Beato, Miguel; Vicent, Guillermo P.
Afiliação
  • Nacht AS; Center for Genomic Regulation (CRG), Barcelona, Spain.
  • Ferrari R; Barcelona Institute for Science and Technology (BIST), Barcelona, Spain.
  • Zaurin R; Center for Genomic Regulation (CRG), Barcelona, Spain.
  • Scabia V; Barcelona Institute for Science and Technology (BIST), Barcelona, Spain.
  • Carbonell-Caballero J; Center for Genomic Regulation (CRG), Barcelona, Spain.
  • Le Dily F; Barcelona Institute for Science and Technology (BIST), Barcelona, Spain.
  • Quilez J; Swiss Institute for Experimental Cancer Research, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
  • Leopoldi A; Center for Genomic Regulation (CRG), Barcelona, Spain.
  • Brisken C; Barcelona Institute for Science and Technology (BIST), Barcelona, Spain.
  • Beato M; Center for Genomic Regulation (CRG), Barcelona, Spain.
  • Vicent GP; Barcelona Institute for Science and Technology (BIST), Barcelona, Spain.
EMBO J ; 38(18): e101426, 2019 09 16.
Article em En | MEDLINE | ID: mdl-31373033
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.
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Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Neoplasias da Mama / Receptores de Progesterona / Proteínas Estimuladoras de Ligação a CCAAT Tipo de estudo: Prognostic_studies Limite: Animals / Female / Humans Idioma: En Revista: EMBO J Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Espanha

Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Neoplasias da Mama / Receptores de Progesterona / Proteínas Estimuladoras de Ligação a CCAAT Tipo de estudo: Prognostic_studies Limite: Animals / Female / Humans Idioma: En Revista: EMBO J Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Espanha