ArticleProceedings of the National Academy of Sciences of the United States of America2013
Estrogen receptor β sustains epithelial differentiation by regulating prolyl hydroxylase 2 transcription.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.
- Genetics of breast cancer bone metastasis: a sequential multistep pattern.Clinical & experimental metastasis · 2014Pooled it
- MORG1 Haploinsufficiency Is Associated with Stage- and Sex-Dependent Renoprotection and Signalling Alterations in Diabetic Kidney Disease.International journal of molecular sciences · 2026Article
- The Role of Estrogen Signaling Pathway and Targeted Therapy Exploration in Urological Tumors.International journal of biological sciences · 2026Review
- Reduction of Prostate Cancer Risk: Role of Frequent Ejaculation-Associated Mechanisms.Cancers · 2025Review
- Transcription factors and hormone receptors: Sex‑specific targets for cancer therapy (Review).Oncology letters · 2025Review
- Regulation of PHD2 by HIF-1α in Erythroid Cells: Insights into Erythropoiesis Under Hypoxia.International journal of molecular sciences · 2025Article
- Acetylcholine in the gingival epithelium drives the pathogenesis of periodontitis.Frontiers in cell and developmental biology · 2025Article
- Estrogen Receptor β4 Regulates Chemotherapy Resistance and Induces Cancer Stem Cells in Triple Negative Breast Cancer.International journal of molecular sciences · 2023Article
- Divergent features of ERβ isoforms in triple negative breast cancer: progress and implications for further research.Frontiers in cell and developmental biology · 2023Review
- Review
- Antitumor effects of aconitine in A2780 cells via estrogen receptor β‑mediated apoptosis, DNA damage and migration.Molecular medicine reports · 2020Article
- ERβ and NFκB-Modulators of Zearalenone-Induced Oxidative Stress in Human Prostate Cancer Cells.Toxins · 2020Article
- Estrogen Receptor Beta (ERβ): A Ligand Activated Tumor Suppressor.Frontiers in oncology · 2020Review
- Estrogen receptor β exerts tumor suppressive effects in prostate cancer through repression of androgen receptor activity.PloS one · 2020Article
- Review
- Article
- Hypoxia Upregulates Estrogen Receptor β in Pulmonary Artery Endothelial Cells in a HIF-1α-Dependent Manner.American journal of respiratory cell and molecular biology · 2018Article
- Article
- Dioscin induces prostate cancer cell apoptosis through activation of estrogen receptor-β.Cell death & disease · 2017Article
- Estrogens in Male Physiology.Physiological reviews · 2017Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Estrogen receptor β (ERβ) promotes the degradation of hypoxia inducible factor 1α (HIF-1α), which contributes to the ability of this hormone receptor to sustain the differentiation of epithelial and carcinoma cells. Although the loss of ERβ and consequent HIF-1 activation occur in prostate cancer with profound consequences, the mechanism by which ERβ promotes the degradation of HIF-1α is unknown. We report that ERβ regulates the ligand (3β-adiol)-dependent transcription of prolyl hydroxylase 2 (PHD2) also known as Egl nine homolog 1 (EGLN1), a 2-oxoglutarate-dependent dioxygenase that hydroxylates HIF-1α and targets it for recognition by the von Hippel-Lindau tumor suppressor and consequent degradation. ERβ promotes PHD2 transcription by interacting with a unique estrogen response element in the 5' UTR of the PHD2 gene that functions as an enhancer. PHD2 itself is critical for maintaining epithelial differentiation. Loss of PHD2 expression or inhibition of its function results in dedifferentiation with characteristics of an epithelial-mesenchymal transition, and exogenous PHD2 expression in dedifferentiated cells can restore an epithelial phenotype. Moreover, expression of HIF-1α in cells that express PHD2 does not induce dedifferentiation but expression of HIF-1α containing mutations in the proline residues that are hydroxylated by PHD2 induces dedifferentiation. These data describe a unique mechanism for the regulation of HIF-1α stability that involves ERβ-mediated transcriptional regulation of PHD2 and they highlight an unexpected role for PHD2 in maintaining epithelial differentiation.
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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.