ArticleMolecular endocrinology (Baltimore, Md.)2013
Progesterone receptor and Stat5 signaling cross talk through RANKL in mammary epithelial cells.
Article in Molecular endocrinology (Baltimore, Md.), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 57 citations in OpenAlex.
- Effect of Bazedoxifene and Conjugated Estrogen (Duavee) on Breast Cancer Risk Biomarkers in High-Risk Women: A Pilot Study.Cancer prevention research (Philadelphia, Pa.) · 2019Trial
- The Role of Progesterone in Elf5 Activation and Milk Component Synthesis for Cell-Cultured Milk Production in MAC-T Cells.Animals : an open access journal from MDPI · 2024Article
- International Union of Basic and Clinical Pharmacology CXIII: Nuclear Receptor Superfamily-Update 2023.Pharmacological reviews · 2023Review
- The High Level of RANKL Improves IκB/p65/Cyclin D1 Expression and Decreases p-Stat5 Expression in Firm Udder of Dairy Goats.International journal of molecular sciences · 2023Article
- Review
- Progesterone Induces Apoptosis and Steroidogenesis in Porcine Placental Trophoblasts.Animals : an open access journal from MDPI · 2022Article
- Hormone and receptor activator of NF-κB (RANK) pathway gene expression in plasma and mammographic breast density in postmenopausal women.Breast cancer research : BCR · 2022Article
- Breast tumor IGF1R regulates cell adhesion and metastasis: alignment of mouse single cell and human breast cancer transcriptomics.Frontiers in oncology · 2022Article
- Prolactin: The Third Hormone in Breast Cancer.Frontiers in endocrinology · 2022Review
- PGRMC1 Inhibits Progesterone-Evoked Proliferation and CaInternational journal of molecular sciences · 2020Article
- Reciprocal fine-tuning of progesterone and prolactin-regulated gene expression in breast cancer cells.Molecular and cellular endocrinology · 2020Article
- Scribble promotes alveologenesis in the pregnant mammary gland for milk production.Reproduction (Cambridge, England) · 2020Article
- Mammary stem cells and progenitors: targeting the roots of breast cancer for prevention.The EMBO journal · 2019Review
- Review
- A mouse model engineered to conditionally express the progesterone receptor-B isoform.Genesis (New York, N.Y. : 2000) · 2018Article
- The Role of Placental Hormones in Mediating Maternal Adaptations to Support Pregnancy and Lactation.Frontiers in physiology · 2018Review
- Posttranslationally modified progesterone receptors direct ligand-specific expression of breast cancer stem cell-associated gene programs.Journal of hematology & oncology · 2017Article
- Review
- Plasma osteoprotegerin and breast cancer risk in BRCA1 and BRCA2 mutation carriers.Oncotarget · 2016Article
- Wnt and Neuregulin1/ErbB signalling extends 3D culture of hormone responsive mammary organoids.Nature communications · 2016Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Progesterone (P4) stimulates proliferation of the mammary epithelium by a mechanism that involves paracrine signaling mediated from progesterone receptor (PR)-positive to neighboring PR-negative cells. Here we used a primary mouse mammary epithelial cell (MEC) culture system to define the molecular mechanism by which P4 regulates the expression of target gene effectors of proliferation including the paracrine factor receptor and activator of nuclear factor κB ligand (RANKL). MECs from adult virgin mice grown and embedded in three-dimensional basement-membrane medium resemble mammary ducts in vivo structurally and with respect to other properties including a heterogeneous pattern of PR expression, P4 induction of RANKL and other target genes in a PR-dependent manner, and a proliferative response to progestin. RANKL was demonstrated to have multiple functional P4-responsive enhancers that bind PR in a hormone-dependent manner as detected by chromatin immunoprecipitation assay. P4 also stimulated recruitment of signal transducer and activator of transcription (Stat)5a to RANKL enhancers through an apparent tethering with PR. Analysis of primary MECs from Stat5a knockout mice revealed that P4 induction of RANKL and a broad range of other PR target genes required Stat5a, as did P4-stimulated cell proliferation. In the absence of Stat5a, PR binding was lost at selective RANKL enhancers but was retained with others, suggesting that Stat5a acts to facilitate PR DNA binding at selective sites and to function as a coactivator with DNA-bound PR at others. These results show that RANKL is a direct PR target gene and that Stat5a has a novel role as a cofactor in PR-mediated transcriptional signaling in the mammary gland.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.