51. Membrane expression of the estrogen receptor ERα is required for intercellular communications in the mammary epithelium
- Author
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Gagniac, Laurine, Rusidzé, Mariam, Boudou, Frederic, Cagnet, Stephanie, Adlanmerini, Marine, Jeannot, Pauline, Gaide, Nicolas, Giton, Frank, Besson, Arnaud, Weyl, Ariane, Gourdy, Pierre, Raymond-Letron, Isabelle, Arnal, Jean-Francois, Brisken, Cathrin, Lenfant, Francoise, and Institut National de la Santé et de la Recherche Médicale (INSERM)
- Subjects
MESH: Signal Transduction ,MESH: Mice, Transgenic ,[SDV]Life Sciences [q-bio] ,Lipoylation ,Mammary gland ,Membrane initiated signaling ,MESH: Lipoylation ,Mice, Transgenic ,Stem cells ,Epithelium ,MESH: Gene Expression Profiling ,Mice ,Mammary Glands, Animal ,MESH: Mice, Inbred C57BL ,Paracrine Communication ,Animals ,MESH: Animals ,MESH: Paracrine Communication ,Paracrine signals ,MESH: Mice ,MESH: Estrogen Receptor alpha ,ECM ,Estradiol ,Gene Expression Profiling ,MESH: Mammary Glands, Animal ,Estrogen Receptor alpha ,Epithelial Cells ,Stem Cells and Regeneration ,MESH: Gene Expression Regulation ,Mice, Inbred C57BL ,MESH: Epithelium ,Gene Expression Regulation ,MESH: Epithelial Cells ,Female ,MESH: Estradiol ,MESH: Female ,Signal Transduction - 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., Summary: Estrogen receptor (ER) α palmitoylation is required for mammary epithelial cell stem cell function, intercellular and intercompartmental communication with altered expression of paracrine factors and impaired ECM remodeling/protease function.
- Published
- 2020