ArticleProceedings of the National Academy of Sciences of the United States of America2007
Amphiregulin is an essential mediator of estrogen receptor alpha function in mammary gland development.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 179 papers, 1 of them a synthesis that pooled it.
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Who cites it
179 citing papers in PubMed, 1 synthesis or guideline pooled it, 312 citations in OpenAlex.
- Abrupt involution induces inflammation, estrogenic signaling, and hyperplasia linking lack of breastfeeding with increased risk of breast cancer.Breast cancer research : BCR · 2019Pooled it
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- Beyond the membrane: rethinking EGFR signaling in physiology and cancer.Cellular and molecular life sciences : CMLS · 2026Review
- Serial Imaging of Tumour and microEnvironment (SITE) platform for live-cellbioRxiv : the preprint server for biology · 2025Article
- The plasma proteome and breast cancer risk.Breast cancer research : BCR · 2025Article
- Amphiregulin and Fibrosis: Existing Evidence and Future Directions.International journal of molecular sciences · 2025Review
- Amphiregulin in Fibrotic Diseases and Cancer.International journal of molecular sciences · 2025Review
- Sensitizing Immune-Refractory Ovarian Tumors via p53 Mutation-Tailored Immunotherapy.bioRxiv : the preprint server for biology · 2025Article
- EGF receptor in organ development, tissue homeostasis and regeneration.Journal of biomedical science · 2025Review
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- Hormone Signaling in Breast Development and Cancer.Advances in experimental medicine and biology · 2025Review
- Breast Morphogenesis: From Normal Development to Cancer.Advances in experimental medicine and biology · 2025Review
- Rat Models of Hormone Receptor-Positive Breast Cancer.Journal of mammary gland biology and neoplasia · 2024Review
- Establishing conditions for the generation and maintenance of estrogen receptor-positive organoid models of breast cancer.Breast cancer research : BCR · 2024Article
- Inhibitory Effect of Jinkui Shenqi Pills on Glucocorticoid-Enhanced Axial Length Elongation in Experimentally Myopic Guinea Pigs.Chinese journal of integrative medicine · 2023Article
- Single-cell and spatial analyses reveal a tradeoff between murine mammary proliferation and lineage programs associated with endocrine cues.Cell reports · 2023Article
- Distinct Requirements for Adaptor Proteins NCK1 and NCK2 in Mammary Gland Development.Journal of mammary gland biology and neoplasia · 2023Article
- Cell type and stage specific transcriptional, chromatin and cell-cell communication landscapes in the mammary gland.Heliyon · 2023Article
- ERBB Receptors and Their Ligands in the Developing Mammary Glands of Different Species: Fifteen Characters in Search of an Author.Journal of mammary gland biology and neoplasia · 2023Review
119 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Most mammary gland development occurs after birth under the control of systemic hormones. Estrogens induce mammary epithelial cell proliferation during puberty via epithelial estrogen receptor alpha (ERalpha) by a paracrine mechanism. Epidermal growth factor receptor (EGFR) signaling has long been implicated downstream of ERalpha signaling, and several EGFR ligands have been described as estrogen-target genes in tumor cell lines. Here, we show that amphiregulin is the unique EGF family member to be transcriptionally induced by estrogen in the mammary glands of puberal mice at a time of exponential expansion of the ductal system. In fact, we find that estrogens induce amphiregulin through the ERalpha and require amphiregulin to induce proliferation of the mammary epithelium. Like ERalpha, amphiregulin is required in the epithelium of puberal mice for epithelial proliferation, terminal end buds formation, and ductal elongation. Subsequent stages, such as side-branching and alveologenesis, are not affected. When amphiregulin(-/-) mammary epithelial cells are in close vicinity to wild-type cells, they proliferate and contribute to all cell compartments of the ductal outgrowth. Thus, amphiregulin is an important paracrine mediator of estrogen function specifically required for puberty-induced ductal elongation, but not for any earlier or later developmental stages.
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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.