ArticleProceedings of the National Academy of Sciences of the United States of America2010
Two distinct mechanisms underlie progesterone-induced proliferation in the mammary gland.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 178 papers, 1 of them a synthesis that pooled it.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
178 citing papers in PubMed, 1 synthesis or guideline pooled it, 301 citations in OpenAlex.
- Tamoxifen and Fertility in Women with Breast Cancer: A Systematic Review on Reproductive Outcomes and Oncological Safety of Treatment Interruption.International journal of molecular sciences · 2025Pooled it
- Trial
- Microglia Rank signaling regulates GnRH neuronal function and the hypothalamic-pituitary-gonadal axis.Science (New York, N.Y.) · 2026Article
- Looking in the Rear-View Mirror: How Lineage Tracing Experiments Redefined Cell Hierarchy in the Mammary Gland.Journal of mammary gland biology and neoplasia · 2026Review
- The Presence of SFRP1 Reduces the High Risk of Metastasis in RANKL-Expressing Canine Mammary Cancers.Animals : an open access journal from MDPI · 2026Article
- Branching out: the diverse roles of stem and progenitor cells in mammary gland development.Journal of mammary gland biology and neoplasia · 2026Review
- Role of DCAF8 in Mammary Ductal Elongation and Branching Morphogenesis.Journal of mammary gland biology and neoplasia · 2026Article
- Rank signaling drives basal cell-lineage infidelity leading to mammary tumorigenesis.Nature communications · 2026Article
- Advances in the intrinsic signaling pathway interactions and clinical translation of HR+/HER2+ breast cancer.Breast cancer (Tokyo, Japan) · 2025Review
- The regulatory role of CDK4/6 inhibitors in tumor immunity and the potential value of tumor immunotherapy (Review).International journal of molecular medicine · 2025Review
- Estrogens and breast cancer.Annals of oncology : official journal of the European Society for Medical Oncology · 2025Review
- Conception and Concern: A Review of Breast Cancer Risk in Assisted Reproductive Technology.International journal of biological sciences · 2025Review
- Hormone Signaling in Breast Development and Cancer.Advances in experimental medicine and biology · 2025Review
- RANK/RANKL Signaling Pathway in Breast Development and Cancer.Advances in experimental medicine and biology · 2025Review
- Classification of Breast Cancer Through the Perspective of Cell Identity Models.Advances in experimental medicine and biology · 2025Review
- Regulatory mechanisms of steroid hormone receptors on gene transcription through chromatin interaction and enhancer reprogramming.Cellular oncology (Dordrecht, Netherlands) · 2024Review
- C/EBPβ deletion in macrophages impairs mammary gland alveolar budding during the estrous cycle.Life science alliance · 2024Article
- Maternal Breast Growth and Body Mass Index Are Associated with Low Milk Production in Women.Nutrients · 2024Article
- Is There a Special Role for Ovarian Hormones in the Pathogenesis of Lobular Carcinoma?Endocrinology · 2024Review
- Causes of Low Milk Supply: The Roles of Estrogens, Progesterone, and Related External Factors.Advances in nutrition (Bethesda, Md.) · 2024Review
118 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The mouse mammary gland develops postnatally under the control of female reproductive hormones. Estrogens and progesterone trigger morphogenesis by poorly understood mechanisms acting on a subset of mammary epithelial cells (MECs) that express their cognate receptors, estrogen receptor alpha (ERalpha) and progesterone receptor (PR). Here, we show that in the adult female, progesterone drives proliferation of MECs in two waves. The first, small wave, encompasses PR(+) cells and requires cyclin D1, the second, large wave, comprises mostly PR(-) cells and relies on the tumor necrosis factor (TNF) family member, receptor activator of NF-kappaB-ligand (RANKL). RANKL elicits proliferation by a paracrine mechanism. Ablation of RANKL in the mammary epithelium blocks progesterone-induced morphogenesis, and ectopic expression of RANKL in MECs completely rescues the PR(-/-) phenotype. Systemic administration of RANKL triggers proliferation in the absence of PR signaling, and injection of a RANK signaling inhibitor interferes with progesterone-induced proliferation. Thus, progesterone elicits proliferation by a cell-intrinsic and a, more important, paracrine mechanism.
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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.