Evidence map›Paper›PMID 37999751›Full record

ArticleJournal of cancer research and clinical oncology2023

EGR3 and estrone are involved in the tamoxifen resistance and progression of breast cancer.

Yu Xie, Xiao Han, Jing Yu, Mengci Yuan, Yan Yan, Junfang Qin, Lan Lan, Yue Wang

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of cancer research and clinical oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
3.4field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 11 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Review
  5. EGR3 Promotes Glioblastoma Cell Growth with Upregulation of MYC and CDK1.International journal of molecular sciences · 2025
    Article
  6. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 4 institutions in 1 country.

Yu XieSchool of Medicine, Nankai University, Tianjin, 300071, China.
Xiao HanState Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Nankai University, Tianjin, 300350, China.
Jing YuSchool of Medicine, Nankai University, Tianjin, 300071, China.
Mengci YuanSchool of Medicine, Nankai University, Tianjin, 300071, China.
Yan YanTianjin Key Laboratory of Oral and Maxillofacial Function Reconstruction, Hospital of Stomatology, Nankai University, Tianjin, 300041, China.
Junfang QinSchool of Medicine, Nankai University, Tianjin, 300071, China.
Lan LanDepartment of Integrated Traditional and Western Medicine, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China.
Yue WangSchool of Medicine, Nankai University, Tianjin, 300071, China. wangyue@nankai.edu.cn.
Nankai University · CNTianjin Medical University Cancer Institute and Hospital · CNTianjin Nankai Hospital · CNTianjin Stomatological Hospital · CN

Funding

the Natural Science Foundation of China 31770968the Natural Science Foundation of China 31800661the Science Fund Project of Tianjin 20JCYBJC01130the Science Fund Project of Tianjin 21JCYBJC00240
6 · The paper itself

Abstract

backgroundTamoxifen (Tam) is an effective treatment for estrogen receptor (ER) positive breast cancer. However, a significant proportion of patients develop resistance under treatment, presenting a therapeutic challenge. The study aims to determine the role of early growth response protein (EGR) 3 in tamoxifen resistance (TamR) and elucidate its molecular mechanism.

methodsTamR cell models were established and NGS was used to screening signaling alternation. Western blot and qRT-PCR were used to analysis the expression of ERα, EGR3, MCL1 and factors associated with apoptosis. CCK8, colony formation and apoptosis assay were used to analysis resistance to Tam. Immunofluorescence, chromatin immunoprecipitation, and dual luciferase assays were used to investigate mechanism of regulation.

resultsWe observed that EGR3, a deeply rooted ERα response factor, showed increased upregulation in response to both estrone (E1) and Tam in TamR cells with elevated level of E1 and ERα expression, indicating a potential connection between EGR3 and TamR. Mechanically, manipulating EGR3 expression revealed that it imparted resistance to Tam through increased expression of the downstream molecule MCL1 (apoptosis suppressor gene) that it regulated. Mechanismly, EGR3 directly binds to the promoter of the anti-apoptotic factor MCL1 gene, facilitating its transcription. Furthermore, apoptosis assays revealed that E1 reduces Tam induced apoptosis by upregulating EGR3 expression. Importantly, clinical public database confirmed the high expression of EGR3 in breast cancer tissue and in Tam-treated patients.

conclusionsThese findings shed light on the novel estrogen/EGR3/MCL1 axis and its role in inducing TamR in ER positive breast cancer. EGR3 emerges as a promising target to overcome TamR. The elucidation of this mechanism holds potential for the development of new therapeutic modalities to overcome endocrine therapy resistance in clinical settings.

Indexed as

Breast NeoplasmsTamoxifenAntineoplastic Agents, HormonalCell ProliferationDrug Resistance, NeoplasmEarly Growth Response Protein 3Estrogen Receptor alphaEstroneFemaleGene Expression Regulation, NeoplasticHumansMCF-7 CellsMyeloid Cell Leukemia Sequence 1 ProteinAntineoplastic Agents, HormonalEarly Growth Response Protein 3EGR3 protein, humanEstrogen Receptor alphaEstroneMyeloid Cell Leukemia Sequence 1 ProteinTamoxifenEGR3Estrogen receptorMCL1ΕstroneΤamoxifen

Identifiers

PMID37999751
PMCPMC11798252
OpenAlexW4388974137

What OpenQuestion holds

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Registered trials

None linked

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.