Biomarker: ER-alpha

Histology type: endometrial stromal tumor

Country: Korea

Region: Seoul

Followed up time :

Subgroup 1 name : positive

Subgroup 1 number: 37

Subgroup 2 name: negative

Subgroup 2 number: 14

Conclusion: Hormone receptors that showed strong expression deserve further evaluation to clarify their importance as a therapeutic target and predictor of treatment response.

Sample type : tissue

Sample method: immunohistochemistry,qRT-PCR

Expression pattern : expression

Expression elevation: To determine the intensity of the immunoreaction, a semi-quantitative scoring system was adopted, and the score was categorized from 0 to 3. The calculation was performed by multiplying this score by the percentage of the total stained width to obtain the final score (0–20 points, negative; 21–80, weakly positive [1+]; 81–180, moderately positive [2+]; and 181–300, strongly positive [3+]).

Statictics: cutoff<47;cutoff>47

Cohort age: 29;22

Funtion Uniprot: Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Essential for MTA1-mediated transcriptional regulation of BRCA1 and BCAS3 (PubMed:17922032).20 Publications Isoform 3 Involved in activation of NOS3 and endothelial nitric oxide production (PubMed:21937726). Isoforms lacking one or several functional domains are thought to modulate transcriptional activity by competitive ligand or DNA binding and/or heterodimerization with the full-length receptor (PubMed:10970861). Binds to ERE and inhibits isoform 1 (PubMed:10970861).2 Publications

UniProt ID: P03372

UniProt Link: https://www.uniprot.org/uniprotkb/P03372/entry

Biological function from UniProt: #Transcription #Transcription regulation

Molecular function from UniProt:

Caution: Was reported to be activated by DDX5. However, this study has been retracted due to concerns of image manipulation.

Miscellaneous: Selective estrogen receptor modulators (SERMs), such as tamoxifen, raloxifene, toremifene, lasofoxifene, clomifene, femarelle and ormeloxifene, have tissue selective agonistic and antagonistic effects on the estrogen receptor (ER). They interfere with the ER association with coactivators or corepressors, mainly involving the AF-2 domain.

Recommended name: Estrogen receptor

Gene name from HGNC: ESR1 (ER-alpha, Era, ESR, NR3A1)

HPA class: Cancer-related genes Disease related genes FDA approved drug targets Human disease related genes Nuclear receptors Transcription factors

AlphaFold DB: P03372

AlphaFold Link: https://alphafold.ebi.ac.uk/entry/P03372

HPA link: https://www.proteinatlas.org/ENSG00000091831-ESR1

Tissue specificity RNA from HPA: Tissue enhanced (cervix, endometrium, fallopian tube)

Tissue expression from HPA: Selective nuclear expression in female genitalia.

Single cell type specificity Cell type enhanced (Glandular and luminal cells, Breast glandular cells, Endometrial stromal cells, Endometrial ciliated cells, Horizontal cells, Skeletal myocytes, Hepatocytes)

Immune cell specificity: Not detected in immune cells

Subcellular summary HPA Located in Nucleoplasm, Vesicles

Cancer prognostic summary HPA Prognostic marker in endometrial cancer (favorable)

Pathology link: https://www.proteinatlas.org/ENSG00000091831-ESR1/pathology

Pathology endo: https://www.proteinatlas.org/ENSG00000091831-ESR1/pathology/endometrial+cancer

OMIM: 133430

OMIM link2: https://www.omim.org/entry/133430

HGNC ID: HGNC:3467

HGNC link: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:3467