Oestrogen receptor α AF-1 and AF-2 domains have cell population-specific functions in the mammary epithelium.
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ICR Authors
Authors
Cagnet, S
Ataca, D
Sflomos, G
Aouad, P
Schuepbach-Mallepell, S
Hugues, H
Krust, A
Ayyanan, A
Scabia, V
Brisken, C
Ataca, D
Sflomos, G
Aouad, P
Schuepbach-Mallepell, S
Hugues, H
Krust, A
Ayyanan, A
Scabia, V
Brisken, C
Document Type
Journal Article
Date
2018-11-09
Date Accepted
2018-10-15
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.
Citation
Nature communications, 2018, 9 (1), pp. 4723 - ?
Source Title
Publisher
NATURE PUBLISHING GROUP
ISSN
2041-1723
eISSN
2041-1723
Collections
Research Team
Endocrine control mechanisms