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Nuclear hormone receptor. Binds estrogens with an affinity similar to that of ESR1/ER-alpha, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent manner.; Lacks ligand binding ability and has no or only very low ERE binding activity resulting in the loss of ligand-dependent transactivation ability.
Gene References into Functions
An association was found between the rs1256032 polymorphism of estrogen receptor beta gene and reduced risk in a Mexican population of developing type 2 diabetes. PMID: 29666032
We identified a homozygous ESR2 variant, c.541_543del p.(Asn181del) in the highly conserved DNA-binding domain of ER-beta in an individual with syndromic 46,XY DSD. Two additional heterozygous missense variants, c.251G>T p.(Gly84Val) and c.1277T>G p.(Leu426Arg), located in the N-terminus and the ligand-binding domain of ER-beta, were found in unrelated, nonsyndromic 46,XY DSD cases. PMID: 29261182
therapeutic activation of ERbeta elicits potent anticancer effects in Triple-negative breast cancer through the induction of a family of secreted proteins known as the cystatins, which function to inhibit canonical TGFbeta signaling and suppress metastatic phenotypes both in vitro and in vivo. PMID: 30257941
ESR2 polymorphisms demonstrate minimal influence on Bone mineral density changes in women. PMID: 29320918
Low ESR2 expression is associated with Tumor Progression in Colorectal Cancer with Familial Adenomatous Polyposis and Sporadic Polyps. PMID: 28681123
The possible role of ESR2 G1730A variant as the risk factor of MI in a young age. PMID: 30036658
TCF21 modulates Steroidogenic factor-1 and estrogen receptor beta expression through the recruitment of USF2 in endometriotic stromal cells. PMID: 30018006
High phosphorylated ESR2 expression is associated with pancreatic ductal adenocarcinoma. PMID: 30046904
FSHR rs6165, not ESR2 rs4986938, could be suggested as a candidate marker to predict poor ovarian response. PMID: 29036809
There was a significant association between ERbeta RsaI and postmenopausal osteoporosis risk in both overall and Asian populations PMID: 29458346
Estrogen receptor beta1 activation accelerates resistance to epidermal growth factor receptor-tyrosine kinase inhibitors in non-small cell lung cancer. PMID: 29328407
Increased cytoplasmic ERbeta1 and nuclear ERbeta2 expression is associated with worse cancer specific outcomes following radical prostatectomy. These findings suggest that tumor ERbeta1 and ERbeta2 staining patterns provide prognostic information on patients treated with radical prostatectomy. PMID: 26804755
ESR2 single nucleotide polymorphism is associated with poor ovarian response in Egyptian women undergoing IVF procedure. PMID: 28825151
ERbeta expression conferred cell sensitivity, as patient-derived AML cells with high levels of ERb were sensitive, whereas cells with low ERb were insensitive to diosmetin. Knockdown of ERb confirmed resistance, whereas overexpression enhanced sensitivity to diosmetin, which was demonstrated to be mediated by reactive oxygen species signaling. PMID: 28835383
Data report for the first time that ERbeta inversely regulates miR-10b and miR-145, which are critical modulators of functional properties, epithelial to mesenchymal transition and extracellular matrix composition of breast cancer cells. ERbeta together with miR-10b and miR-145, are key players for the initiation of breast cancer cell aggressiveness. PMID: 28797712
the mRNA expression levels of ERbeta isoforms are downregulated in sporadic colorectal cancer and in FAP individuals. T3/T4 tumours also presented decreased expression of ERbeta. Additionally, the expression levels of ERbeta1 and ERbeta5 were associated with the probability of disease-free survival. PMID: 29132333
factors that regulate the alternative splicing of ERs remain unknown. We demonstrate novel evidence supporting a potential biological feedback loop where 17beta-estradiol regulates the RNA-binding protein Nova1, which, in turn, regulates the alternative splicing of ERbeta PMID: 29031089
A dual role of the association between AGO2 and ERbeta in luminal-like breast cancer cells in the nucleus and the cytoplasm, for the regulation of gene expression at both the transcriptional and post-transcriptional level. PMID: 29017520
We found higher nuclear (n)ERalpha and nERbeta5 and lower cytoplasmic (c)ERalpha expression in advanced ovarian cancers. Lower ERbeta1 expression was also detected in high grade cancers. Loss of nERalpha and cERbeta2 expression were observed in clear cell histological subtypes. Higher nERbeta5 and lower cERbeta5 expression were associated with serous/clear cell subtypes, poor disease-free and overall survival. PMID: 28859612
We found little overall difference in the DNA methylation of the ESR2 5'-flanking region in individuals with autism compared with normal individuals. PMID: 28299627
our data reveal a novel mechanism for ERbeta's anti-proliferative and pro-apoptotic effects in breast cancer cells involving p53 and epigenetic changes in histone methylation that underlie gene regulation of these cellular activities. PMID: 28577282
loss of ERbeta function acts in collaboration with p53 inactivation to induce early onset of mammary tumors with spindle cell morphology and more basal-like characteristics. PMID: 28673316
Low levels of ESR2 is associated with metastasis in triple-negative breast cancer. PMID: 28583190
Findings from the systematic review and meta-analysis suggest that rs1256120 of ESR2 is unlikely to be a predisposing or disease-modifying genetic risk factor for adolescent idiopathic scoliosis. PMID: 27755497
High concentrations of DINCH urinary metabolites activate human ESR2 receptors. PMID: 29421333
Tumor ERbeta1 expression was available for 911 breast cancer patients and was not associated with ESR2 genotypes. High tumor ERbeta1 expression is a marker of good prognosis in breast cancer, especially among chemotherapy-treated patients, but not in endocrine therapy-treated patients. PMID: 27810901
Targeting ERbeta with selective agonists might affect Hodgkins lymphoma cell proliferation and tumor growth via a mechanism that brings into play DRAM2-dependent autophagic cascade. PMID: 28052027
ERbeta might be the target protein of arctigenin responsible for inhibition of mTORC1 activation and resultant prevention of Th17 cell differentiation and colitis development. PMID: 27863380
Data suggest that the ERalpha-H19-BIK signaling axis plays an important role in promoting breast cancer cell chemoresistance. PMID: 27845892
fulvestrant up-regulated ERbeta in ERalpha+/ERbeta+ breast cancer and in triple negative ERbeta+ breast cancers (ERalpha-/ERbeta+) PMID: 27486755
ERbeta plays a crucial role in the cell behavior and extracellular matrix composition of the highly aggressive MDA-MB-231 cells. PMID: 27179695
Study provides evidence for a critical role of ESR2 in radio-resistance of in head and neck squamous cell carcinoma, and that SMR3A might serve as a surrogate marker for active ESR2 signaling. PMID: 28166815
This study demonstrated that ESR2 but not ESR1 minor alleles were associated with lower cognitive performance in elderly women with an indication of a gene-gene interaction with APOEepsilon4. And also found indications for gene-environment interactions of ESR2 with traffic-related air pollution exposure on cognitive performance. PMID: 27629499
LY500307 is a highly selective estrogen receptor beta agonist, which loses its selectivity at high dose and leads to undesirable suppression of total testosterone concentration. PMID: 27136911
ERbeta ubiquitination, protein turnover, and inhibition of breast cancer is regulated by tyrosine phosphorylation PMID: 27323858
ERbeta in both normal and cancerous colon epithelial cells upregulates miRNA-205, which subsequently reduces PROX1 through direct interaction with its 3'UTR PMID: 27283988
Membrane estrogen receptor beta and GPER signaling mediate cellular responses to environmentally relevant concentrations of CdCl2 and NaAsO2 in lung adenocarcinoma cells. PMID: 27071941
C-Jun and CREB are recruited to ESR2 or CYP19A1 promoter by IGF-I stimulation. PMID: 26899323
increases in ERbeta and p53 immunoreactivity were significantly correlated with the incidence of metastasis and/or recurrence in endometrial endometrioid carcinoma PMID: 29190668
Low estrogen receptor beta is associated with triple-negative breast cancer. PMID: 26871946
The variation at rs10144225 in ESR2 was associated with salt-sensitive blood pressure (SSBP) in premenopausal women (estrogen-replete) and not in men or postmenopausal women (estrogen-deplete). Inappropriate aldosterone levels on a liberal salt diet may mediate the SSBP. PMID: 28938457
Data suggest that 17-beta-estradiol/ESR2 signaling counteracts TNFA-induced, inflammation-mediated apoptosis of vascular endothelial cells in a mechanism that requires NOTCH1-mediated Akt phosphorylation. (ESR2 = estrogen receptor 2; TNFA = tumor necrosis factor-alpha; NOTCH1 = Notch homolog 1, translocation-associated protein) PMID: 28893903
Expression of ERbeta and p53 significantly correlated with age and advanced cancer stages, and the p53-negative EOGC was associated with favorable outcomes. PMID: 27781410
Our data suggest that oestrogens stimulated osteogenic differentiation in human dental pulp cells and that this action is mediated principally through the ERbeta isoform PMID: 29031686
ESR2 may modify the interaction between negative life events and MDD in the Chinese Han menopausal females. PMID: 27814959
Results show that ERb is upregulated in bladder malignant tissue, and its expression is associated with muscle-invasive disease. PMID: 27324053
estrogen may play a role in androgen-independent prostate cancer cell proliferation through a novel pathway, involving ERbeta-mediated activation of beta-catenin. PMID: 27107935
ERbeta immunoreactivity was markedly present in all the cases of Merkel cell carcinoma examined. significant correlation with Ki-67 labeling index and Bcl-2 score suggest that ERbeta could be associated with regulation of both cell proliferation and apoptosis in MCCs. PMID: 27343835
Germline ESR2 mutation is associated with medullary thyroid carcinoma. PMID: 26945007
Exposure to the combination of 100 muM genistein and 10 nM calcitriol reduced the number of proliferative cells to control levels, increased ERb and VDR expression, and reduced extracellular acidification (40%) as well as respiratory activity (70%), primarily in MG-63 cells..strong overexpression SGPL1, which irreversibly degrades sphingosine-1-phosphate thereby, generating ethanolamine PMID: 28125641
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Subcellular Location
Nucleus.
Protein Families
Nuclear hormone receptor family, NR3 subfamily
Tissue Specificity
[Isoform 1]: Expressed in testis and ovary, and at a lower level in heart, brain, placenta, liver, skeletal muscle, spleen, thymus, prostate, colon, bone marrow, mammary gland and uterus. Also found in uterine bone, breast, and ovarian tumor cell lines, b