Affinage

ESR1

Estrogen receptor · UniProt P03372

Length
595 aa
Mass
66.2 kDa
Annotated
2026-06-09
100 papers in source corpus 21 papers cited in narrative 21 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ESR1 encodes ERα, a ligand-regulated nuclear transcription factor that controls estrogen-driven gene programs by either binding estrogen response elements (EREs) directly or tethering to other transcription factors at non-ERE sites; in vivo loss of its DNA-binding function shows that a substantial fraction of estradiol-regulated transcripts are governed through tethered, non-ERE mechanisms (PMID:19812388). ERα can heterodimerize with ERβ, which restrains ERα-mediated transcription, and both receptors co-cluster in discrete ligand-induced nuclear foci (PMID:12351687); both can independently transduce the estradiol proliferative signal in mammary epithelium (PMID:14762170). A recurrent mechanistic theme is cooperative DNA binding with SP1: the ligand-dependent ERα–SP1 complex activates the TNFα promoter to drive caspase-3–dependent apoptosis in one context (PMID:23733894) and the Slc2a4/GLUT4 promoter to promote glucose-transporter expression in adipocytes (PMID:30275758). ERα activity is gated by post-translational modification — monoubiquitination is required for E2-induced Ser118 phosphorylation, extranuclear AKT activation, cyclin D1 promoter activation, IGF-1R association, and proliferation (PMID:21356307). ESR1 expression is itself epigenetically silenced through a ZEB1/DNMT3B/HDAC1 complex that hypermethylates the ESR1 promoter, and relieving this silencing restores antiestrogen sensitivity (PMID:28383555). In metastatic breast cancer, somatic ligand-binding-domain hotspot mutations (Y537S, D538G) confer constitutive ligand-independent activity and endocrine-therapy resistance (PMID:27986707); these alleles drive FOXA1-dependent cistrome reprogramming and neomorphic transcriptional programs that remodel cell adhesion and promote metastasis (PMID:29438694, PMID:35078818), and additional acquired mutations at residue F404 disrupt fulvestrant pi-stacking to cause selective drug resistance (PMID:37982575). Beyond its transcriptional roles, Esr1-expressing neurons in the lateral hypothalamus signal aversion via projections to the lateral habenula (PMID:37349481).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2003 Medium

    Established that ERα does not act alone but forms functional heterodimers with ERβ that modulate its transcriptional output and co-organize into defined nuclear chromatin foci.

    Evidence Live-cell imaging of GFP-tagged receptors with deletion mutants and colocalization with chromatin-remodeling markers

    PMID:12351687

    Open questions at the time
    • Endogenous heterodimer occupancy at native target genes not mapped
    • Mechanism of ERβ inhibition of ERα not resolved
  2. 2004 High

    Resolved whether ERα and ERβ have distinct roles in estrogen-driven proliferation, showing ERα initiates the proliferative signal while ERβ governs ERα nuclear recycling and responsiveness.

    Evidence BrdU incorporation and immunofluorescence in WT and ERβ-knockout mice under multiple ligand conditions

    PMID:14762170

    Open questions at the time
    • Molecular basis of ERα nuclear loss/return unknown
    • Target genes mediating proliferation not identified
  3. 2009 High

    Separated direct ERE-driven transcription from tethered non-ERE regulation in vivo, quantifying that a large fraction of estradiol-regulated genes use DNA-binding-independent mechanisms.

    Evidence KIKO DNA-binding-deficient knock-in mouse with genome-wide expression profiling across three genotypes

    PMID:19812388

    Open questions at the time
    • Identity of tethering transcription factors at non-ERE sites not enumerated
    • Tissue specificity beyond uterus unaddressed
  4. 2011 Medium

    Defined monoubiquitination as a required upstream switch coupling ERα to Ser118 phosphorylation, extranuclear AKT signaling, IGF-1R association, and proliferation.

    Evidence Site-directed mutagenesis of ubiquitination sites with signaling, reporter, Co-IP, and proliferation readouts

    PMID:21356307

    Open questions at the time
    • E3 ligase mediating monoubiquitination not identified
    • Single-lab functional readouts
  5. 2013 Medium

    Demonstrated ERα can cooperate with SP1 to drive a pro-apoptotic transcriptional program, broadening ERα function beyond proliferation.

    Evidence Co-IP, TNFα promoter reporter with SP1-site deletions, and SP1-inhibitor treatment in Hep3B cells

    PMID:23733894

    Open questions at the time
    • Context-dependence (overexpression in ER-negative cells) limits generalization
    • Endogenous relevance not shown
  6. 2015 High

    Identified ligand-binding-domain hotspot mutations as the mechanistic basis of acquired endocrine resistance via constitutive ligand-independent ERα activity.

    Evidence Mutation characterization across >900 patients with in vitro constitutive-activity assays and xenograft antagonist-sensitivity testing

    PMID:27986707

    Open questions at the time
    • Allele-specific downstream programs not yet resolved at this stage
    • Structural basis of constitutive activity not detailed
  7. 2017 High

    Established a transcriptional/epigenetic silencing mechanism controlling ESR1 expression itself through a ZEB1/DNMT3B/HDAC1 promoter complex linked to antiestrogen sensitivity.

    Evidence ChIP, Co-IP of the repressor complex, siRNA, bisulfite sequencing, and xenograft assays

    PMID:28383555

    Open questions at the time
    • Upstream signals activating ZEB1 in this context not defined
    • Reversibility in patients not tested
  8. 2018 High

    Showed mutant ERα acquires neomorphic, allele-specific chromatin recruitment driving pro-metastatic transcription rather than merely mimicking liganded receptor.

    Evidence ChIP-seq cistrome mapping and genetic screens across breast cancer models with clinical mutations

    PMID:29438694

    Open questions at the time
    • Pioneer factor driving neomorphic recruitment not yet pinpointed in this study
    • Therapeutic targeting of neomorphic sites unaddressed
  9. 2022 High

    Mechanistically linked hotspot mutations to FOXA1-driven cistrome reprogramming that remodels adhesion gene programs to promote circulating tumor cell cluster formation and metastasis.

    Evidence Genome-edited mutant models with cistrome/transcriptome profiling, in vivo CTC analysis, and five clinical cohorts

    PMID:35078818

    Open questions at the time
    • How FOXA1 is redirected by LBD mutations remains mechanistically incomplete
    • Generalizability across mutation alleles partially explored
  10. 2022 High

    Extended mutant-ERα reprogramming to ER-binding-independent outputs, including basal cytokeratin induction via a progesterone-receptor-orchestrated insulated neighborhood and paracrine immune mediator changes.

    Evidence Genome-edited models with ATAC-seq/ChIP-seq, single-cell RNA-seq, and clinical samples

    PMID:35440136

    Open questions at the time
    • Causal contribution of PR insulated neighborhood to phenotype not isolated
    • Immune crosstalk consequences for therapy untested
  11. 2023 High

    Defined a non-transcription-factor neural role, showing Esr1+ lateral hypothalamic neurons projecting to the lateral habenula encode aversion and a persistent aversive state.

    Evidence Patch-seq classification, optogenetic activation, large-scale recordings, and behavioral assays

    PMID:37349481

    Open questions at the time
    • Whether ERα transcriptional activity is required for this circuit function not established
    • Ligand dependence of the neural phenotype unknown
  12. 2024 Medium

    Resolved a structural determinant of drug binding, identifying ERα F404 as a pi-stacking residue whose mutation selectively abolishes fulvestrant efficacy while sparing oral degraders.

    Evidence In silico structural modeling, in vitro single/compound mutant models, and clinical ctDNA sequencing from PlasmaMATCH

    PMID:37982575

    Open questions at the time
    • Crystallographic confirmation of the pi-stacking bond not provided
    • Clinical frequency and prognostic impact of F404 mutations not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • How ERα PTM codes, cofactor tethering, and mutation-driven cistrome reprogramming are integrated into a unified, predictively targetable mechanism remains unresolved.
  • No structural model unifying neomorphic chromatin recruitment with LBD mutation
  • E3 ligases governing ERα ubiquitination states incompletely mapped
  • Link between transcriptional ERα biology and Esr1+ neuronal function unexplored

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 4 GO:0003677 DNA binding 2
Localization
GO:0005634 nucleus 3 GO:0005654 nucleoplasm 1
Pathway
R-HSA-1643685 Disease 4 R-HSA-4839726 Chromatin organization 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-162582 Signal Transduction 1
Partners
ESR2FOXA1IGF-1RSP1ZEB1ZNF143

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 ERα and ERβ form functional heterodimers when coexpressed, and ERβ exhibits an inhibitory action on ERα-mediated gene expression; both receptors colocalize in the same discrete nuclear clusters upon ligand activation, with cluster formation requiring at least the latter part of AF-1, the DNA-binding domain, nuclear matrix binding domain, and AF-2/ligand-binding domain of ERα. Live-cell imaging with GFP-tagged fusion proteins, deletion mutant analysis, colocalization with hyperacetylated histone H4 and Brg-1 (chromatin remodeling complex component) Molecular endocrinology Medium 12351687
2004 ERα receives the estrogen proliferation signal in mammary epithelial cells and initiates DNA synthesis, then is lost from the nucleus; ERβ facilitates the return of ERα to the nucleus and restores responsiveness to estradiol. Both ERα and ERβ can independently mediate estradiol-induced proliferation. BrdUrd incorporation assay in WT and ERβ-knockout mice treated with E2, tamoxifen, or ERβ-specific agonist; immunofluorescence with specific antibodies for ERα and ERβ localization Proceedings of the National Academy of Sciences of the United States of America High 14762170
2009 ERα directly binds to the estrogen-responsive element (ERE) DNA motif to regulate a distinct set of uterine genes; loss of ERα DNA-binding activity (KIKO knock-in mouse) reveals that 38% of wild-type E2-regulated transcripts are also regulated via non-ERE tethered mechanisms, and an entirely unique set of 1438 transcripts is regulated only in the KIKO context. Canonical pathways including Jak/Stat are regulated similarly by ERE and non-ERE pathways, while Wnt/β-catenin pathway members differ. In vivo knock-in mouse model (KIKO) lacking ERα DNA-binding function; microarray gene expression profiling; comparison of WT, KIKO, and αERKO genotypes Molecular endocrinology High 19812388
2011 ERα monoubiquitination is required for E2-induced ERα phosphorylation at Ser118, transcriptional activity, extranuclear AKT activation, cyclin D1 promoter activation, and cell proliferation; mutation of ERα monoubiquitination sites also disrupts E2-induced ERα association with IGF-1R. Site-directed mutagenesis of ERα monoubiquitination sites; cell proliferation assays; western blotting for phospho-Ser118, AKT activation; cyclin D1 promoter reporter assays; co-immunoprecipitation for IGF-1R interaction Cellular signalling Medium 21356307
2013 ERα (ESR1) overexpression in ER-negative Hep3B cells induces apoptosis via a ligand-dependent interaction with SP1 protein; the ERα-SP1 complex binds proximal and distal SP1 sites in the TNFα gene promoter, activating TNFα expression and downstream caspase-3 activation. Deletion of SP1 binding sites in the TNFα promoter abolished ERα-mediated promoter activity. DNA fragmentation assay; flow cytometry; western blotting for active caspase-3 and TNFα; co-immunoprecipitation of ERα and SP1; TNFα promoter reporter assays with SP1-site deletions; mithramycin (SP1 inhibitor) treatment Journal of molecular endocrinology Medium 23733894
2015 ESR1 somatic mutations clustered in the ligand-binding domain (LBD) confer ligand-independent ER transcriptional activity in metastatic breast cancer; these gain-of-function mutations (e.g., Y537S, D538G) promote estrogen-independent tumor growth and confer partial to full resistance to endocrine therapies including aromatase inhibitors and fulvestrant. Characterization of ESR1 mutations from >900 patients; in vitro functional assays for constitutive activity; in vivo xenograft models; comparison of sensitivity to ER antagonists including fulvestrant and AZD9496 Cancer discovery High 27986707
2017 ZEB1 represses ESR1 transcription by forming a ZEB1/DNMT3B/HDAC1 complex on the ESR1 promoter, leading to DNA hypermethylation and silencing of ERα; siRNA depletion of ZEB1 causes ESR1 promoter demethylation and restores ERα expression and antiestrogen sensitivity. Chromatin immunoprecipitation (ChIP); co-immunoprecipitation of ZEB1/DNMT3B/HDAC1 complex; siRNA knockdown; bisulfite sequencing; reporter assays; nude mouse xenograft model Cell death & disease High 28383555
2018 ESR1 LBD mutations exhibit both ligand-independent functions that mimic estradiol-bound wild-type ER and allele-specific neomorphic (neomorphic/gain-of-function) chromatin recruitment properties that promote a pro-metastatic transcriptional program; genome-wide ER binding site analysis identified mutant ER-unique recruitment sites mediating allele-specific transcriptional programs. ChIP-seq for genome-wide ER binding; genetic screens for essential genes; transcriptional network analysis in breast cancer models with clinically relevant ER mutations Cancer cell High 29438694
2018 ESR1 activation in adipocytes increases nuclear SP1 protein content, the SP1/ESR1 complex formation, and SP1 binding to the Slc2a4 gene promoter, resulting in increased Slc2a4/GLUT4 expression; this ESR1/SP1 cooperative mechanism is specific to ESR1 (not ESR2) and is demonstrated via immunoprecipitation of SP1/ESR1 complex and EMSA. Western blotting; immunoprecipitation of SP1/ESR1 complex; EMSA (electrophoretic mobility shift assay) for SP1 binding to Slc2a4 promoter; ESR1 agonist (PPT) and antagonist; siRNA knockdown International journal of medical sciences Medium 30275758
2019 Estradiol stimulates adipogenesis and Slc2a4/GLUT4 expression via an ESR1-dependent, CEBPA-mediated pathway; ESR1 silencing abrogates E2-induced nuclear CEBPA content, Slc2a4/GLUT4 expression, and GLUT4 translocation to the cell membrane. siRNA-mediated Esr1 silencing in 3T3-L1 adipocytes; western blotting; RT-qPCR; GLUT4 translocation assay Molecular and cellular endocrinology Medium 31100494
2020 RON kinase is hyperactivated in ESR1 Y537S mutant breast cancer cells and interacts with IGF-1R; RON/PI3K hyperactivity is regulated by mutant ER (reduced by endocrine therapies) and RON inhibition combined with endocrine therapy decreases organoid growth and reduces metastasis in an ESR1 Y537S PDX model. Proteomic kinome analysis; phospho-immunoblot; pharmacological and genetic inhibition of RON and IGF-1R; organoid growth assays; in vivo PDX metastatic model British journal of cancer Medium 33257837
2021 ESR1 ChIP-seq in human hepatocytes and liver tissue identifies both ligand-dependent and ligand-independent (unliganded) ESR1 genomic binding sites with distinct genomic localization, pathway enrichment, and cofactor co-localization patterns; ligand-free ESR1 shows co-enrichment with ZNF143 and regulates CYP genes involved in drug metabolism. ChIP-seq in human liver samples and hepatocytes with/without 17β-estradiol; pathway enrichment analysis; cofactor co-localization analysis International journal of molecular sciences Medium 33540646
2022 ESR1 hotspot mutations (Y537S, D538G) reprogram the ER cistrome via de novo FOXA1-driven chromatin remodeling and secondary transcriptional regulation; these mutations alter desmosome/gap junction genes and the TIMP3/MMP axis, functionally enhancing cell-cell contacts while decreasing cell-extracellular matrix adhesion, thereby promoting metastatic CTC cluster formation. Genome-edited ESR1 mutant cell models; transcriptomic and cistrome profiling; in vivo CTC cluster analysis; five independent breast cancer cohorts; Wnt/ER co-targeting experiments Cancer research High 35078818
2022 ESR1 mutant cells show induction of basal cytokeratins (BCKs) independent of ER binding, associated with chromatin reprogramming centered on a progesterone receptor-orchestrated insulated neighborhood; ESR1 mutant tumors also show elevated S100A8/S100A9 immune mediators via tumor-stroma paracrine crosstalk. Genome-edited ESR1 mutant cell models; ATAC-seq/ChIP-seq for chromatin reprogramming; single-cell RNA-seq from metastatic tumors; analysis of clinical samples Nature communications High 35440136
2022 TRIM4 E3 ligase catalyzes K48-linked polyubiquitination of SET at K150 and K172, promoting SET proteasomal degradation; loss of SET releases p53 and PP2A, which in turn promote ESR1 gene transcription and mRNA stability, thereby enhancing ERα expression and tamoxifen sensitivity. In vitro and in vivo ubiquitination assays; co-immunoprecipitation of TRIM4-SET (mapping to RING/B-box and SET C-terminus); domain mapping; western blotting; siRNA/overexpression experiments Advanced science Medium 35843886
2023 Esr1-expressing (Esr1+) neurons in the lateral hypothalamic area (LHA) projecting to the lateral habenula (LHb) induce aversion and a behaviorally persistent aversive state upon repeated optogenetic activation; these neurons show sex-specific shifts in intrinsic bursting properties following unpredictable mild shocks in female mice, associated with stress sensitivity. Patch-seq multimodal classification; optogenetic stimulation; large-scale neural recordings; behavioral assays; electrophysiology Nature neuroscience High 37349481
2024 ESR1 F404 residue contributes to fulvestrant binding to ERα through a pi-stacking bond; acquired F404L/I/V mutations (in cis with activating mutations) disrupt this bond, causing overt resistance to fulvestrant but not to oral ERα degraders; compound mutations D538G+F404L and E380Q+F404L confer fulvestrant resistance in vitro. In silico structural modeling of F404-fulvestrant pi-stacking; in vitro cell line models with single and compound ESR1 mutations; sequencing of baseline and end-of-treatment ctDNA from clinical trial (PlasmaMATCH); pharmacological testing with oral ERα degraders Cancer discovery Medium 37982575
2009 ERα suppresses expression of its variant ERα36 in an estrogen-independent manner by acting on the ERα36 promoter; ERα36 itself can release this suppression. Promoter cloning; transient co-transfection reporter assays; transcription initiation site mapping FEBS letters Low 19328202
2008 ERα activation (via estradiol or ESR1 agonist PPT) increases pancreatic beta-cell insulin content, insulin gene expression, and insulin release through ERK1/2 signaling; this effect is absent in ERα-knockout mice and is mimicked by bisphenol-A. ERα and ERβ agonists; ERαKO and ERβKO mouse models; ERK1/2 pathway inhibition; gene expression analysis PloS one Medium 18446233
2017 ESR1 (ERα) activation by E2 induces binding of HIF1A to the VEGFA gene promoter in adipocytes, promoting VEGFA expression; ESR1-selective agonist (PPT) mimics this effect, while ESR1 siRNA knockdown decreases VEGFA and prevents E2-mediated modulation; ESR1 total body knockout female mice show lower VEGFA in adipose tissue. ChIP for HIF1A binding to VEGFA promoter; siRNA knockdown of ESR1; ESR1 agonist/antagonist treatment in 3T3-L1 cells; ESR1 total body knockout mice Scientific reports Medium 29196658
2012 δEF1 represses ERα transcription by binding to the E2-box on the ERα promoter, an effect induced by E2 via ERα-dependent PI3K or NF-κB pathway; elevated δEF1 reduces ERα levels and confers tamoxifen resistance, while δEF1 depletion restores ERα expression and tamoxifen sensitivity. Luciferase reporter assays with E2-box promoter constructs; ChIP for δEF1 binding; siRNA knockdown; overexpression; western blotting PloS one Medium 23285017

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 Estrogen signaling: a subtle balance between ER alpha and ER beta. Molecular interventions 572 14993442
2015 ESR1 mutations—a mechanism for acquired endocrine resistance in breast cancer. Nature reviews. Clinical oncology 544 26122181
2001 A novel ER alpha-mannosidase-like protein accelerates ER-associated degradation. EMBO reports 365 11375934
2016 Activating ESR1 Mutations Differentially Affect the Efficacy of ER Antagonists. Cancer discovery 323 27986707
2008 Pancreatic insulin content regulation by the estrogen receptor ER alpha. PloS one 315 18446233
2007 Estrogen receptor alpha (ESR1) gene amplification is frequent in breast cancer. Nature genetics 284 17417639
2018 Allele-Specific Chromatin Recruitment and Therapeutic Vulnerabilities of ESR1 Activating Mutations. Cancer cell 221 29438694
2019 ESR1 mutations in breast cancer. Cancer 209 31318440
2005 Estrogen and the brain: beyond ER-alpha, ER-beta, and 17beta-estradiol. Annals of the New York Academy of Sciences 129 16024756
2021 ESR1 mutations and therapeutic resistance in metastatic breast cancer: progress and remaining challenges. British journal of cancer 121 34621045
2004 Estrogen receptors ER alpha and ER beta in proliferation in the rodent mammary gland. Proceedings of the National Academy of Sciences of the United States of America 114 14762170
2006 Estrogen receptor-alpha (ER-alpha) and defects in uterine receptivity in women. Reproductive biology and endocrinology : RB&E 113 17118173
2010 A review of estrogen receptor alpha gene (ESR1) polymorphisms, mood, and cognition. Menopause (New York, N.Y.) 109 20616674
2025 First-Line Camizestrant for Emerging ESR1-Mutated Advanced Breast Cancer. The New England journal of medicine 91 40454637
2019 ESR1 alterations and metastasis in estrogen receptor positive breast cancer. Journal of cancer metastasis and treatment 90 31106278
2009 Estrogen receptor-alpha (ER-alpha) suppresses expression of its variant ER-alpha 36. FEBS letters 74 19328202
2017 ZEB1 induces ER-α promoter hypermethylation and confers antiestrogen resistance in breast cancer. Cell death & disease 72 28383555
2004 Estrogen and the brain: beyond ER-alpha and ER-beta. Experimental gerontology 72 15582272
2023 CircPVT1 promotes ER-positive breast tumorigenesis and drug resistance by targeting ESR1 and MAVS. The EMBO journal 71 37009655
2017 Estrogen receptor 1 (ESR1) regulates VEGFA in adipose tissue. Scientific reports 71 29196658
2004 Differential regulation of estrogen receptor (ER)alpha and ERbeta in primate mammary gland. The Journal of clinical endocrinology and metabolism 69 15507513
2014 Estrogen receptor (ER) α mutations in breast cancer: hidden in plain sight. Breast cancer research and treatment 67 24487689
2017 Detection of Activating Estrogen Receptor Gene (ESR1) Mutations in Single Circulating Tumor Cells. Clinical cancer research : an official journal of the American Association for Cancer Research 62 28679775
2022 Hotspot ESR1 Mutations Are Multimodal and Contextual Modulators of Breast Cancer Metastasis. Cancer research 61 35078818
2022 ESR1 mutant breast cancers show elevated basal cytokeratins and immune activation. Nature communications 60 35440136
2019 miR-4324-RACGAP1-STAT3-ESR1 feedback loop inhibits proliferation and metastasis of bladder cancer. International journal of cancer 59 30511377
2007 Association between estrogen receptor alpha (ESR1) gene polymorphisms and severe preeclampsia. Hypertension research : official journal of the Japanese Society of Hypertension 58 17510501
2002 Expression of ER-alpha and ER-beta in the hamster ovary: differential regulation by gonadotropins and ovarian steroid hormones. Endocrinology 56 12021204
2009 DNA hypermethylation of ESR1 and PGR in breast cancer: pathologic and epidemiologic associations. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 54 19861523
2002 Colocalization and ligand-dependent discrete distribution of the estrogen receptor (ER)alpha and ERbeta. Molecular endocrinology (Baltimore, Md.) 53 12351687
2022 ESR1 activating mutations: From structure to clinical application. Biochimica et biophysica acta. Reviews on cancer 49 36336145
2019 ESR1 mutations: a new biomarker in breast cancer. Expert review of molecular diagnostics 48 31188645
2009 Potentially functional polymorphisms in ESR1 and breast cancer risk: a meta-analysis. Breast cancer research and treatment 48 19760036
2013 Chromatin and epigenetic determinants of estrogen receptor alpha (ESR1) signaling. Molecular and cellular endocrinology 45 23684889
2014 ESR1 and ESR2 differentially regulate daily and circadian activity rhythms in female mice. Endocrinology 44 24735329
2003 Expression of estrogen receptor alpha (ER alpha) in the rat temporomandibular joint. The anatomical record. Part A, Discoveries in molecular, cellular, and evolutionary biology 44 12973717
2018 The Impact of ESR1 Mutations on the Treatment of Metastatic Breast Cancer. Hormones & cancer 43 29736566
2020 Intrinsic and Extrinsic Factors Governing the Transcriptional Regulation of ESR1. Hormones & cancer 40 32592004
2019 Estradiol stimulates adipogenesis and Slc2a4/GLUT4 expression via ESR1-mediated activation of CEBPA. Molecular and cellular endocrinology 39 31100494
2014 Xenoestrogens alter estrogen receptor (ER) α intracellular levels. PloS one 37 24586459
2005 Polymorphisms in ER-alpha gene interact with estrogen receptor status in breast cancer survival. Clinical cancer research : an official journal of the American Association for Cancer Research 36 15709176
2005 Expression of estrogen receptor ESR1 and its 46-kDa variant in the gubernaculum testis. Biology of reproduction 36 15944240
2023 ESR1 fusions and therapeutic resistance in metastatic breast cancer. Frontiers in oncology 35 36686845
2020 Hormonal modulation of ESR1 mutant metastasis. Oncogene 35 33323970
2013 Estrogen receptor α (ESR1) over-expression mediated apoptosis in Hep3B cells by binding with SP1 proteins. Journal of molecular endocrinology 35 23733894
2010 Estrogen receptor alpha (ESR-1) associations with psychological traits in women with PMDD and controls. Journal of psychiatric research 35 20172536
2014 ESR1 and ESR2 gene polymorphisms are associated with human reproduction outcomes in Brazilian women. Journal of ovarian research 34 25526766
2011 17β-Estradiol-induced cell proliferation requires estrogen receptor (ER) α monoubiquitination. Cellular signalling 34 21356307
2010 Estrogen receptor 1 gene (ESR1) is associated with restrictive anorexia nervosa. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 34 20375995
2018 Estrogen Receptor-Alpha (ESR1) Governs the Lower Female Reproductive Tract Vulnerability to Candida albicans. Frontiers in immunology 33 29881378
2009 Selective disruption of ER{alpha} DNA-binding activity alters uterine responsiveness to estradiol. Molecular endocrinology (Baltimore, Md.) 33 19812388
2008 Oestrogen receptor gene (ESR1) amplification is frequent in endometrial carcinoma and its precursor lesions. The Journal of pathology 33 18720455
2024 ESR1 F404 Mutations and Acquired Resistance to Fulvestrant in ESR1-Mutant Breast Cancer. Cancer discovery 32 37982575
2023 Esr1+ hypothalamic-habenula neurons shape aversive states. Nature neuroscience 32 37349481
2021 Disrupted PGR-B and ESR1 signaling underlies defective decidualization linked to severe preeclampsia. eLife 31 34709177
2019 Aberrant DNA methylation suppresses expression of estrogen receptor 1 (ESR1) in ovarian endometrioma. Journal of ovarian research 31 30728052
2022 Mutual exclusivity of ESR1 and TP53 mutations in endocrine resistant metastatic breast cancer. NPJ breast cancer 30 35538119
2019 ESR1 mutations in metastatic lobular breast cancer patients. NPJ breast cancer 29 30820448
2018 Estrogen Receptor 1 (ESR1) Enhances Slc2a4/GLUT4 Expression by a SP1 Cooperative Mechanism. International journal of medical sciences 29 30275758
2017 Estrogen receptor (ESR1) mutation in bone metastases from breast cancer. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 29 28799536
2011 ESR1 in myocardial infarction. Clinica chimica acta; international journal of clinical chemistry 29 22061094
2007 Estrogen Receptor 1 gene (ESR1) variants in Alzheimer's disease. Results of a meta-analysis. Aging clinical and experimental research 29 17446729
2003 ER-alpha variants and the cardiovascular effects of hormone replacement therapy. Pharmacogenomics 29 12718718
2023 Formononetin ameliorates airway inflammation by suppressing ESR1/NLRP3/Caspase-1 signaling in asthma. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 28 37922653
2018 Implications of ESR1 Mutations in Hormone Receptor-Positive Breast Cancer. Current treatment options in oncology 28 29666928
2022 The E3 Ligase TRIM4 Facilitates SET Ubiquitin-Mediated Degradation to Enhance ER-α Action in Breast Cancer. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 27 35843886
2018 Frequent ESR1 and CDK Pathway Copy-Number Alterations in Metastatic Breast Cancer. Molecular cancer research : MCR 27 30355675
2021 Daidzein Induces Intrinsic Pathway of Apoptosis along with ER α/β Ratio Alteration and ROS Production. Asian Pacific journal of cancer prevention : APJCP 25 33639680
2021 Preexisting Somatic Mutations of Estrogen Receptor Alpha (ESR1) in Early-Stage Primary Breast Cancer. JNCI cancer spectrum 24 33937624
2020 RON signalling promotes therapeutic resistance in ESR1 mutant breast cancer. British journal of cancer 24 33257837
2010 DNA methylation of ESR-1 and N-33 in colorectal mucosa of patients with ulcerative colitis (UC). Epigenetics 23 20505342
2015 Association between estrogen receptor 1 (ESR1) genetic variations and cancer risk: a meta-analysis. Journal of B.U.ON. : official journal of the Balkan Union of Oncology 22 25778331
2014 Association of polymorphisms in estrogen receptors (ESR1 and ESR2) with male infertility: a meta-analysis and systematic review. Journal of assisted reproduction and genetics 22 24647635
2020 Association of estrogen receptor gene variants (ESR1 and ESR2) with polycystic ovary syndrome in Tunisia. Gene 21 32169631
2018 HSD3B2, HSD17B1, HSD17B2, ESR1, ESR2 and AR expression in infertile women with endometriosis. Ginekologia polska 21 29664547
2016 ESR1 and its antagonist fulvestrant in pituitary adenomas. Molecular and cellular endocrinology 21 28043824
2015 Impact of ESR1 Gene Polymorphisms on Migraine Susceptibility: A Meta-Analysis. Medicine 21 26334887
2014 The influence of ESR1 rs9340799 and ESR2 rs1256049 polymorphisms on prostate cancer risk. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 21 24859835
2005 ESR1 and APOE gene polymorphisms, serum lipids, and hormonal replacement therapy. Maturitas 21 16242874
2012 RNA-based determination of ESR1 and HER2 expression and response to neoadjuvant chemotherapy. Annals of oncology : official journal of the European Society for Medical Oncology 20 23131391
2021 ESR1 hotspot mutations in endometrial stromal sarcoma with high-grade transformation and endocrine treatment. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 19 34961764
2012 An advanced Electron Spin Resonance (ESR) spin-trapping and LC/(ESR)/MS technique for the study of lipid peroxidation. International journal of molecular sciences 19 23203086
2021 Evaluation of endocrine resistance using ESR1 genotyping of circulating tumor cells and plasma DNA. Breast cancer research and treatment 17 34101078
2020 Estrogen receptor (ESR1 and ESR2)-mediated activation of eNOS-NO-cGMP pathway facilitates high altitude acclimatization. Nitric oxide : biology and chemistry 17 32544536
2019 Characterizing the selectivity of ER α-glucosidase inhibitors. Glycobiology 17 30976784
2012 δEF1 down-regulates ER-α expression and confers tamoxifen resistance in breast cancer. PloS one 17 23285017
2021 ESR1 ChIP-Seq Identifies Distinct Ligand-Free ESR1 Genomic Binding Sites in Human Hepatocytes and Liver Tissue. International journal of molecular sciences 16 33540646
2020 Interaction of Coumarin Phytoestrogens with ERα and ERβ: A Molecular Dynamics Simulation Study. Molecules (Basel, Switzerland) 16 32150902
2017 Immunohistochemical expression of ER-α and PR in papillary thyroid carcinoma. Ecancermedicalscience 16 28717394
2014 The ESR1 gene in unexplained recurrent spontaneous abortion. Systems biology in reproductive medicine 16 24568551
2021 Transcriptional regulation of CYP19A1 expression in chickens: ESR1, ESR2 and NR5A2 form a functional network. General and comparative endocrinology 15 34710471
2019 Association of rs2234693 and rs9340799 polymorphisms of ESR1 gene in breast cancer of Mexican population. Journal of B.U.ON. : official journal of the Balkan Union of Oncology 15 31786857
2014 Association between estrogen receptora gene (ESR1) PvuII (T/C) and XbaI (A/G) polymorphisms and premature ovarian failure risk: evidence from a meta-analysis. Journal of assisted reproduction and genetics 15 25428437
2012 MTA1 expression correlates significantly with ER-alpha methylation in breast cancer. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 15 22644675
2022 IL-27 promotes decidualization via the STAT3-ESR/PGR regulatory axis. Journal of reproductive immunology 14 35430461
2021 The rs9340799 polymorphism of the estrogen receptor alpha (ESR1) gene and its association with breast cancer susceptibility. Scientific reports 14 34545128
2020 The crosstalk between IGF-1R and ER-α in the proliferation and anti-inflammation of nucleus pulposus cells. European review for medical and pharmacological sciences 14 32572901
2017 Are We Ready to Use ESR1 Mutations in Clinical Practice? Breast care (Basel, Switzerland) 14 29234250
2016 Estrogen Receptor Alpha (ESR1)-Dependent Regulation of the Mouse Oviductal Transcriptome. PloS one 14 26808832
2013 ESR1 gene amplification in endometrial carcinomas: a clinicopathological analysis. Anticancer research 14 24023309

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