Oestrogen receptor α AF-1 and AF-2 domains have cell population-specific functions in the mammary epithelium

Stéphanie Cagnet, Dalya Ataca, George Sflomos, Patrick Aouad, Sonia Schuepbach-Mallepell, Henry Hugues, Andrée Krust, Ayyakkannu Ayyanan, Valentina Scabia and Cathrin Brisken ()
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Stéphanie Cagnet: Swiss Institute for Experimental Cancer Research, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne
Dalya Ataca: Swiss Institute for Experimental Cancer Research, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne
George Sflomos: Swiss Institute for Experimental Cancer Research, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne
Patrick Aouad: Swiss Institute for Experimental Cancer Research, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne
Sonia Schuepbach-Mallepell: University of Lausanne
Henry Hugues: University Hospital of Lausanne
Andrée Krust: Institut de Génétique et de Biologie Moléculaire et Cellulaire (CNRS UMR7104; INSERM U596; ULP, Collège de France) and Institut Clinique de la Souris
Ayyakkannu Ayyanan: Swiss Institute for Experimental Cancer Research, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne
Valentina Scabia: Swiss Institute for Experimental Cancer Research, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne
Cathrin Brisken: Swiss Institute for Experimental Cancer Research, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne

Nature Communications, 2018, vol. 9, issue 1, 1-15

Abstract: Abstract Oestrogen receptor α (ERα) is a transcription factor with ligand-independent and ligand-dependent activation functions (AF)-1 and -2. Oestrogens control postnatal mammary gland development acting on a subset of mammary epithelial cells (MECs), termed sensor cells, which are ERα-positive by immunohistochemistry (IHC) and secrete paracrine factors, which stimulate ERα-negative responder cells. Here we show that deletion of AF-1 or AF-2 blocks pubertal ductal growth and subsequent development because both are required for expression of essential paracrine mediators. Thirty percent of the luminal cells are ERα-negative by IHC but express Esr1 transcripts. This low level ERα expression through AF-2 is essential for cell expansion during puberty and growth-inhibitory during pregnancy. Cell-intrinsic ERα is not required for cell proliferation nor for secretory differentiation but controls transcript levels of cell motility and cell adhesion genes and a stem cell and epithelial mesenchymal transition (EMT) signature identifying ERα as a key regulator of mammary epithelial cell plasticity.

Date: 2018
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DOI: 10.1038/s41467-018-07175-0

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