title: Progesterone drives mammary secretory differentiation via RankL-mediated induction of Elf5 in luminal progenitor cells.
abstract: Progesterone-RankL paracrine signaling has been proposed as a driver of stem cell expansion in the mammary gland, and Elf5 is essential for the differentiation of mammary epithelial progenitor cells. We demonstrate that Elf5 expression is induced by progesterone and that Elf5 and progesterone cooperate to promote alveolar development. The progesterone receptor and Elf5 are expressed in a mutually exclusive pattern, and we identify RankL as the paracrine mediator of the effects of progesterone on Elf5 expression in CD61+ progenitor cells and their consequent differentiation. Blockade of RankL action prevented progesterone-induced side branching and the expansion of Elf5(+) mature luminal cells. These findings describe a mechanism by which steroid hormones can produce the expansion of steroid hormone receptor-negative mammary epithelial cells.
authors: Cancer Research Program, Garvan Institute of Medical Research, 348 Victoria Street, and St Vincent's Hospital Clinical School, University of New South Wales, Darlinghurst NSW 2010, Australia.
authors: Heather J
authors: HJ
authors: Lee
authors: David
authors: D
authors: Gallego-Ortega
authors: Anita
authors: A
authors: Ledger
authors: Daniel
authors: D
authors: Schramek
authors: Purna
authors: P
authors: Joshi
authors: Maria M
authors: MM
authors: Szwarc
authors: Christina
authors: C
authors: Cho
authors: John P
authors: JP
authors: Lydon
authors: Rama
authors: R
authors: Khokha
authors: Josef M
authors: JM
authors: Penninger
authors: Christopher J
authors: CJ
authors: Ormandy
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000235:genetics; D008321:Mammary Glands, Animal / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D011374:Progesterone / Q000494:pharmacology*; D053245:RANK Ligand / Q000378:metabolism / Q000494:pharmacology* / Q000502:physiology; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D013234:Stem Cells / Q000378:metabolism* / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics / Q000502:physiology
chemical_list: D004268:DNA-Binding Proteins; C500759:Elf5 protein, mouse; D053245:RANK Ligand; D011980:Receptors, Progesterone; D014157:Transcription Factors; D011374:Progesterone