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Oestrogen receptor α AF-1 and AF-2 domains have cell population-specific functions in the mammary epithelium
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Oestrogen receptor α AF-1 and AF-2 domains have cell population-specific functions in the mammary epithelium
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Journal Article
Oestrogen receptor α AF-1 and AF-2 domains have cell population-specific functions in the mammary epithelium
2018
Overview
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.
Oestrogen receptors α (ERα) are expressed in a subset of mammary epithelial cells. Here, the authors identify cells with low-ERα protein levels and show that distinct cell populations have distinct requirements for the AF1 and AF2 domains of the ERα, and ERα acts in a biphasic manner dependent on developmental stage.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/31
/ 13/51
/ 14
/ 14/19
/ 14/32
/ 38
/ 38/91
/ 49
/ 59
/ Animals
/ Biochemistry, Molecular Biology
/ Domains
/ Endocrine System - metabolism
/ Epithelial Cells - metabolism
/ Estrogen Receptor alpha - chemistry
/ Estrogen Receptor alpha - genetics
/ Estrogen Receptor alpha - metabolism
/ Female
/ Humanities and Social Sciences
/ Ligands
/ Mammary Glands, Animal - growth & development
/ Mammary Glands, Animal - metabolism
/ Puberty
/ Science
