Molecule Information

General Information of the Molecule (ID: Mol04312)

• Name: Estrogen receptor (ESR1) ,Homo sapiens
• Synonyms: ER-alpha; Estradiol receptor; Nuclear receptor subfamily 3 group A member 1
• Molecule Type: Protein
• Gene Name: ESR1
• Gene ID: 2099
• Sequence:
  MTMTLHTKASGMALLHQIQGNELEPLNRPQLKIPLERPLGEVYLDSSKPAVYNYPEGAAY
  EFNAAAAANAQVYGQTGLPYGPGSEAAAFGSNGLGGFPPLNSVSPSPLMLLHPPPQLSP
  F LQPHGQQVPYYLENEPSGYTVREAGPPAFYRPNSDNRRQGGRERLASTNDKGSMAMES
  AK ETRYCAVCNDYASGYHYGVWSCEGCKAFFKRSIQGHNDYMCPATNQCTIDKNRRKSC
  QAC RLRKCYEVGMMKGGIRKDRRGGRMLKHKRQRDDGEGRGEVGSAGDMRAANLWPSPL
  MIKR SKKNSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELV
  HMINW AKRVPGFVDLTLHDQVHLLECAWLEILMIGLVWRSMEHPGKLLFAPNLLLDRNQ
  GKCVEG MVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKD
  HIHRVLD KITDTLIHLMAKAGLTLQQQHQRLAQLLLILSHIRHMSNKGMEHLYSMKCKN
  VVPLYDLL LEMLDAHRLHAPTSRGGASVEETDQSHLATAGSTSSHSLQKYYITGEAEGF
  PATV
• Function: Nuclear hormone receptor. The steroid hormones and theirreceptors are involved in the regulation of eukaryotic gene expressionand affect cellular proliferation and differentiation in targettissues. Ligand-dependent nuclear transactivation involves eitherdirect homodimer binding to a palindromic estrogen response element sequence or association with other DNA-binding transcriptionfactors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational changeallowing subsequent or combinatorial association with multiproteincoactivator complexes through LXXLL motifs of their respectivecomponents. Mutual transrepression occurs between the estrogen receptor and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcriptionfrom the IL6 promoter and displace RELA/p65 and associated coregulatorsfrom the promoter. Recruited to the NF-kappa-B response element of theCCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-Bcomponents RELA/p65 and NFKB1/p50 on ERE sequences. Can also actsynergistically with NF-kappa-B to activate transcription involvingrespective recruitment adjacent response elements; the functioninvolves CREBBP. Can activate the transcriptional activity of TFF1.Also mediates membrane-initiated estrogen signaling involving variouskinase cascades. Essential for MTA1-mediated transcriptional regulationof BRCA1 and BCAS3 . Maintains neuronal survival inresponse to ischemic reperfusion injury when in the presence ofcirculating estradiol .{ECO:0000250|UniProtKB:P06211, ECO:0000269|PubMed:10681512,ECO:0000269|PubMed:10816575, ECO:0000269|PubMed:11477071,ECO:0000269|PubMed:11682626, ECO:0000269|PubMed:14764652,ECO:0000269|PubMed:15078875, ECO:0000269|PubMed:15891768,ECO:0000269|PubMed:16043358, ECO:0000269|PubMed:16617102,ECO:0000269|PubMed:16684779, ECO:0000269|PubMed:17922032,ECO:0000269|PubMed:17932106, ECO:0000269|PubMed:18247370,ECO:0000269|PubMed:19350539, ECO:0000269|PubMed:20074560,ECO:0000269|PubMed:20705611, ECO:0000269|PubMed:21330404,ECO:0000269|PubMed:22083956, ECO:0000269|PubMed:37478846,ECO:0000269|PubMed:7651415, ECO:0000269|PubMed:9328340}.; [Isoform 3]: Involved in activation of NOS3 and endothelialnitric oxide production . Isoforms lacking one orseveral functional domains are thought to modulate transcriptionalactivity by competitive ligand or DNA binding and/or heterodimerizationwith the full-length receptor . Binds to ERE andinhibits isoform 1 . {ECO:0000269|PubMed:10970861,ECO:0000269|PubMed:21937726}.
• Uniprot ID: ESR1_HUMAN
• Ensembl ID: ENSG0000009183125
• HGNC ID: HGNC:3467

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  ADTT: Aberration of the Drug's Therapeutic Target

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Fulvestrant

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Breast adenocarcinoma [ICD-11: 2C60.1] [1]

• Resistant Disease: Breast adenocarcinoma [ICD-11: 2C60.1]
• Resistant Drug: Fulvestrant
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: MCF7 LTLT cells; Breast; Homo sapiens (Human); N.A.
• In Vivo Model: NSG mice model; Mus musculus
• Experiment for Molecule Alteration: GeneSeq assay; Western blot assay
• Experiment for Drug Resistance: Tumor growth assay; Histological assay
• Mechanism Description: In a model of AI-resistant breast cancer without ESR1 mutations, LAS alone or combined with PAL inhibited the growth of primary tumors more effectively than FUL. In addition, the LAS/PAL combination significantly reduced bone metastases. These results suggest that LAS alone or in combination with a CDK4/6i may be a promising therapy for patients with AI-resistant breast cancer, independent of ESR1 mutations. These results also suggest that LAS might be effective in tumors that express low levels of ERalpha.

References

• Ref 1: Lasofoxifene as a potential treatment for aromatase inhibitor-resistant ER-positive breast cancer. Breast Cancer Res. 2024 Jun 7;26(1):95.