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

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State: Public
Version: Final published version
Serval ID
serval:BIB_316E60D35F70
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Oestrogen receptor α AF-1 and AF-2 domains have cell population-specific functions in the mammary epithelium.
Journal
Nature communications
Author(s)
Cagnet S., Ataca D., Sflomos G., Aouad P., Schuepbach-Mallepell S., Hugues H., Krust A., Ayyanan A., Scabia V., Brisken C.
ISSN
2041-1723 (Electronic)
ISSN-L
2041-1723
Publication state
Published
Issued date
09/11/2018
Peer-reviewed
Oui
Volume
9
Number
1
Pages
4723
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
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.
Keywords
Animals, Cell Proliferation, Endocrine System/metabolism, Epithelial Cells/cytology, Epithelial Cells/metabolism, Epithelium/metabolism, Estrogen Receptor alpha/chemistry, Estrogen Receptor alpha/genetics, Estrogen Receptor alpha/metabolism, Female, Gene Expression Regulation, Mammary Glands, Animal/growth & development, Mammary Glands, Animal/metabolism, Mice, Inbred C57BL, Phenotype, Pregnancy, Protein Domains, RNA, Messenger/genetics, RNA, Messenger/metabolism, Steroids/metabolism, Structure-Activity Relationship
Pubmed
Web of science
Open Access
Yes
Create date
20/11/2018 10:07
Last modification date
20/08/2019 14:16
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