生物
旁分泌信号
雌激素受体
细胞生物学
内科学
乳腺
内分泌学
雌激素受体α
雌激素
受体
生物化学
遗传学
医学
癌症
乳腺癌
作者
Laurine Gagniac,Mariam Rusidzé,Frédéric Boudou,Stéphanie Cagnet,Marine Adlanmérini,Pauline Jeannot,Nicolas Gaide,Frank Giton,Arnaud Besson,Ariane Weyl,Pierre Gourdy,Isabelle Raymond‐Letron,Jean‐François Arnal,Cathrin Brisken,Françoise Lenfant
出处
期刊:Development
[The Company of Biologists]
日期:2020-03-01
卷期号:147 (5)
被引量:7
摘要
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.
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