ArticleProceedings of the National Academy of Sciences of the United States of America2008
Identification of a gain-of-function mutation of the prolactin receptor in women with benign breast tumors.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 97 citations in OpenAlex.
- Defining Multiple Fibroadenomas: A Systematic Review of Clinical Characteristics and Management.The breast journal · 2026Pooled it
- Recurrent bilateral giant breast fibroadenomas with a somatic PIK3CA p.G106V mutation: case report and review of current evidence.BMC women's health · 2025Review
- Changes in the mammary gland during aging and its links with breast diseases.Acta biochimica et biophysica Sinica · 2023Review
- Identification of prolactin receptor variants with diverse effects on receptor signalling.Journal of molecular endocrinology · 2023Article
- Functional regulations between genetic alteration-driven genes and drug target genes acting as prognostic biomarkers in breast cancer.Scientific reports · 2022Article
- Prolactin receptor gene transcriptional control, regulatory modalities relevant to breast cancer resistance and invasiveness.Frontiers in endocrinology · 2022Review
- The role ofTranslational cancer research · 2020Article
- Orchestration of signaling by structural disorder in class 1 cytokine receptors.Cell communication and signaling : CCS · 2020Article
- Positive association between progestins and the evolution of multiple fibroadenomas in 72 women.Endocrine connections · 2020Article
- Association of prolactin receptor (PRLR) variants with prolactinomas.Human molecular genetics · 2019Article
- Truncating Prolactin Receptor Mutations Promote Tumor Growth in Murine Estrogen Receptor-Alpha Mammary Carcinomas.Cell reports · 2016Article
- Prolactin Signaling Stimulates Invasion via Na(+)/H(+) Exchanger NHE1 in T47D Human Breast Cancer Cells.Molecular endocrinology (Baltimore, Md.) · 2016Article
- Exome Sequencing of SLC30A2 Identifies Novel Loss- and Gain-of-Function Variants Associated with Breast Cell Dysfunction.Journal of mammary gland biology and neoplasia · 2015Article
- The prolactin receptor: Diverse and emerging roles in pathophysiology.Journal of clinical & translational endocrinology · 2015Review
- A Residue Quartet in the Extracellular Domain of the Prolactin Receptor Selectively Controls Mitogen-activated Protein Kinase Signaling.The Journal of biological chemistry · 2015Article
- New insights in prolactin: pathological implications.Nature reviews. Endocrinology · 2015Review
- Modeling prolactin actions in breast cancer in vivo: insights from the NRL-PRL mouse.Advances in experimental medicine and biology · 2015Article
- STAT signaling in mammary gland differentiation, cell survival and tumorigenesis.Molecular and cellular endocrinology · 2014Review
- Eliminative signaling by Janus kinases: role in the downregulation of associated receptors.Journal of cellular biochemistry · 2014Review
- Mutant prolactin receptor and familial hyperprolactinemia.The New England journal of medicine · 2013Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
There is currently no known genetic disease linked to prolactin (Prl) or its receptor (PrlR) in humans. Given the essential role of this hormonal system in breast physiology, we reasoned that genetic anomalies of Prl/PrlR genes may be related to the occurrence of breast diseases with high proliferative potential. Multiple fibroadenomas (MFA) are benign breast tumors which appear most frequently in young women, including at puberty, when Prl has well-recognized proliferative actions on the breast. In a prospective study involving 74 MFA patients and 170 control subjects, we identified four patients harboring a heterozygous single nucleotide polymorphism in exon 6 of the PrlR gene, encoding Ile(146)-->Leu substitution in its extracellular domain. This sole substitution was sufficient to confer constitutive activity to the receptor variant (PrlR(I146L)), as assessed in three reconstituted cell models (Ba/F3, HEK293 and MCF-7 cells) by Prl-independent (i) PrlR tyrosine phosphorylation, (ii) activation of signal transducer and activator of transcription 5 (STAT5) signaling, (iii) transcriptional activity toward a Prl-responsive reporter gene, and (iv) cell proliferation and protection from cell death. Constitutive activity of PrlR(I146L) in the breast sample from a patient was supported by increased STAT5 signaling. This is a unique description of a functional mutation of the PrlR associated with a human disease. Hallmarks of constitutive activity were all reversed by a specific PrlR antagonist, which opens potential therapeutic approaches for MFA, or any other disease that could be associated with this mutation in future.
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