Oestrogen receptor α AF-1 and AF-2 domains have cell population-specific functions in the mammary epithelium.
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Date
2018-11-09ICR Author
Author
Cagnet, S
Ataca, D
Sflomos, G
Aouad, P
Schuepbach-Mallepell, S
Hugues, H
Krust, A
Ayyanan, A
Scabia, V
Brisken, C
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
Endocrine System
Epithelium
Mammary Glands, Animal
Epithelial Cells
Animals
Mice, Inbred C57BL
Steroids
Estrogen Receptor alpha
RNA, Messenger
Cell Proliferation
Gene Expression Regulation
Structure-Activity Relationship
Pregnancy
Phenotype
Female
Protein Domains
Research team
Endocrine control mechanisms
Language
eng
Date accepted
2018-10-15
License start date
2018-11-09
Citation
Nature communications, 2018, 9 (1), pp. 4723 - ?
Publisher
NATURE PUBLISHING GROUP