Membrane expression of the estrogen receptor ERα is required for intercellular communications in the mammary epithelium.
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Embargo End Date
ICR Authors
Authors
Gagniac, L
Rusidzé, M
Boudou, F
Cagnet, S
Adlanmerini, M
Jeannot, P
Gaide, N
Giton, F
Besson, A
Weyl, A
Gourdy, P
Raymond-Letron, I
Arnal, J-F
Brisken, C
Lenfant, F
Rusidzé, M
Boudou, F
Cagnet, S
Adlanmerini, M
Jeannot, P
Gaide, N
Giton, F
Besson, A
Weyl, A
Gourdy, P
Raymond-Letron, I
Arnal, J-F
Brisken, C
Lenfant, F
Document Type
Journal Article
Date
2020-03-11
Date Accepted
2020-02-06
Abstract
17β-Estradiol induces the postnatal development of mammary gland and influences breast carcinogenesis by binding to the estrogen receptor ERα. ERα acts as a transcription factor but also elicits rapid signaling through a fraction of ERα expressed at the membrane. Here, we have used the C451A-ERα mouse model mutated for the palmitoylation site to understand how ERα membrane signaling affects mammary gland development. Although the overall structure of physiological mammary gland development is slightly affected, both epithelial fragments and basal cells isolated from C451A-ERα mammary glands failed to grow when engrafted into cleared wild-type fat pads, even in pregnant hosts. Similarly, basal cells purified from hormone-stimulated ovariectomized C451A-ERα mice did not produce normal outgrowths. Ex vivo, C451A-ERα basal cells displayed reduced matrix degradation capacities, suggesting altered migration properties. More importantly, C451A-ERα basal cells recovered in vivo repopulating ability when co-transplanted with wild-type luminal cells and specifically with ERα-positive luminal cells. Transcriptional profiling identified crucial paracrine luminal-to-basal signals. Altogether, our findings uncover an important role for membrane ERα expression in promoting intercellular communications that are essential for mammary gland development.
Citation
Development (Cambridge, England), 2020, 147 (5)
Source Title
Publisher
COMPANY BIOLOGISTS LTD
ISSN
0950-1991
eISSN
1477-9129
Collections
Research Team
Endocrine control mechanisms