ArticleEndocrinology2019
Differential Actions of Estrogen Receptor α and β via Nongenomic Signaling in Human Prostate Stem and Progenitor Cells.
Article in Endocrinology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 31 citations in OpenAlex.
- Molecular regulation of estrogen receptors and recent advances on ERα36 splice variant in prostate cancer.Journal of the Endocrine Society · 2026Article
- Tracing the Evolution of Sex Hormones and Receptor-Mediated Immune Microenvironmental Differences in Prostate and Bladder Cancers: From Embryonic Development to Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Review
- 17β-Estradiol Abrogates TNF-α-Induced Human Brain Vascular Pericyte Migration by Downregulating miR-638 via ER-β.International journal of molecular sciences · 2024Article
- Article
- Hallmarks of sex bias in immuno-oncology: mechanisms and therapeutic implications.Nature reviews. Cancer · 2024Article
- Sex steroid hormone residues in milk and their potential risks for breast and prostate cancer.Frontiers in nutrition · 2024Review
- Membrane estrogen receptor α signaling modulates the sensitivity to estradiol treatment in a dose- and tissue- dependent manner.Scientific reports · 2023Article
- Review
- The emerging role of estrogen's non-nuclear signaling in the cardiovascular disease.Frontiers in cardiovascular medicine · 2023Review
- Membrane-Initiated Estrogen, Androgen, and Progesterone Receptor Signaling in Health and Disease.Endocrine reviews · 2022Review
- Therapeutic Targeting of Ovarian Cancer Stem Cells Using Estrogen Receptor Beta Agonist.International journal of molecular sciences · 2022Article
- Visualization of the protein-protein interactions of hormone receptors in hormone-dependent cancer research.Endocrine oncology (Bristol, England) · 2022Review
- EZH2 Mediates Proliferation, Migration, and Invasion Promoted by Estradiol in Human Glioblastoma Cells.Frontiers in endocrinology · 2022Article
- The Visualization of Protein-Protein Interactions in Breast Cancer: Deployment Study in Pathological Examination.Acta histochemica et cytochemica · 2021Review
- Hormonally Regulated Myogenic miR-486 Influences Sex-specific Differences in Cancer-induced Skeletal Muscle Defects.Endocrinology · 2021Article
- Steroid Receptors in Breast Cancer: Understanding of Molecular Function as a Basis for Effective Therapy Development.Cancers · 2021Review
- Review
- Combined Effects of Different Endocrine-Disrupting Chemicals (EDCs) on Prostate Gland.International journal of environmental research and public health · 2021Review
- The HeyL-Aromatase Axis Promotes Cancer Stem Cell Properties by Endogenous Estrogen-Induced Autophagy in Castration-Resistant Prostate Cancer.Frontiers in oncology · 2021Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Human prostate stem and progenitor cells express estrogen receptor (ER)α and ERβ and exhibit proliferative responses to estrogens. In this study, membrane-initiated estrogen signaling was interrogated in human prostate stem/progenitor cells enriched from primary epithelial cultures and stem-like cell lines from benign and cancerous prostates. Subcellular fractionation and proximity ligation assays localized ERα and ERβ to the cell membrane with caveolin-1 interactions. Exposure to 17β-estradiol (E2) for 15 to 60 minutes led to sequential phosphorylation of signaling molecules in MAPK and AKT pathways, IGF1 receptor, epidermal growth factor receptor, and ERα, thus documenting an intact membrane signalosome that activates diverse downstream cascades. Treatment with an E2-dendrimer conjugate or ICI 182,870 validated E2-mediated actions through membrane ERs. Overexpression and knockdown of ERα or ERβ in stem/progenitor cells identified pathway selectivity; ERα preferentially activated AKT, whereas ERβ selectively activated MAPK cascades. Furthermore, prostate cancer stem-like cells expressed only ERβ, and brief E2 exposure activated MAPK but not AKT cascades. A gene subset selectively regulated by nongenomic E2 signaling was identified in normal prostate progenitor cells that includes BGN, FOSB, FOXQ1, and MAF. Membrane-initiated E2 signaling rapidly modified histone methyltransferases, with MLL1 cleavage observed downstream of phosphorylated AKT and EZH2 phosphorylation downstream of MAPK signaling, which may jointly modify histones to permit rapid gene transcription. Taken together, the present findings document ERα and ERβ membrane-initiated signaling in normal and cancerous human prostate stem/progenitor cells with differential engagement of downstream effectors. These signaling pathways influence normal prostate stem/progenitor cell homeostasis and provide novel therapeutic sites to target the elusive prostate cancer stem cell population.
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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.