Evidence map›Paper›PMID 12897156›Full record

ArticleMolecular and cellular biology2003

Estrogen receptor-dependent proteasomal degradation of the glucocorticoid receptor is coupled to an increase in mdm2 protein expression.

H Karimi Kinyamu, Trevor K Archer

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

Article in Molecular and cellular biology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
72citing papers in PubMed, 2 pooled it
6.9field-weighted citation impact, top 3% 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

72 citing papers in PubMed, 2 syntheses or guidelines pooled it, 157 citations in OpenAlex.

  1. Pooled it
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  11. Glucocorticoid Receptor: A Multifaceted Actor in Breast Cancer.International journal of molecular sciences · 2021
    Review
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12 more citing papers are in PubMed but not listed here.

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

2 authors at 1 institution in 1 country.

H Karimi KinyamuChromatin and Gene Expression Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA.
Trevor K Archer
National Institute of Environmental Health Sciences · US

Funding

Transcriptional Functions of Nuclear Receptors in Cancer CellsZIAES071006 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI ARCHER, TREVOR KEITH · 2009 to 2025
$58.0M
Transcriptional Functions of Nuclear Receptors in Cancer CellsZ01ES071006 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI ARCHER, TREVOR KEITH · 1999 to 2008
$6.9M
6 · The paper itself

Abstract

Glucocorticoids and estrogens regulate a number of vital physiological processes. We developed a model breast cancer cell line, MCF-7 M, to examine potential mechanisms by which the ligand-bound estrogen receptor (ER) regulates glucocorticoid receptor (GR)-mediated transcription. MCF-7 cells, which endogenously express ERalpha, were stably transfected with mouse mammary tumor virus promoter-luciferase (MMTV-LUC) reporter and GR expression constructs. Our results demonstrate that treatment with estrogen agonists (17beta-estradiol [E2], diethylstilbestrol, genistein), but not antagonists (tamoxifen or raloxifene), for 48 h inhibits GR-mediated MMTV-LUC transcription and chromatin remodeling. Furthermore, estrogen agonists inhibit glucocorticoid induction of p21 mRNA and protein levels, suggesting that the repressive effect applies to other GR-regulated genes and proteins in MCF-7 cells. Importantly, GR transcriptional activity is compromised because treatment with estrogen agonists down regulates GR protein levels. The protein synthesis inhibitor cycloheximide and the proteasome inhibitor MG132 block E2-mediated decrease in GR protein levels, suggesting that estrogen agonists down regulate the GR via the proteasomal degradation pathway. In support of this, we demonstrate that E2-mediated GR degradation is coupled to an increase in p53 and its key regulator protein Mdm2 (murine double minute 2), an E3 ubiquitin ligase shown to target the GR for degradation. Using the chromatin immunoprecipitation assay, we demonstrate an E2-dependent recruitment of ERalpha to the Mdm2 promoter, suggesting a role of ER in the regulation of Mdm2 protein expression and hence the enhanced GR degradation in the presence of estrogen agonists. Our study shows that cross talk between the GR and ER involves multiple signaling pathways, indicative of the mechanistic diversity within steroid receptor-regulated transcription.

Indexed as

Nuclear ProteinsBlotting, WesternChromatinCysteine EndopeptidasesDose-Response Relationship, DrugDown-RegulationEstrogen AntagonistsEstrogensGlucocorticoidsHumansLigandsLuciferasesMultienzyme ComplexesPrecipitin TestsProteasome Endopeptidase ComplexProto-Oncogene ProteinsChromatinCysteine EndopeptidasesEstrogen AntagonistsEstrogensGlucocorticoidsHRAS protein, humanLigandsLuciferasesMDM2 protein, humanMultienzyme ComplexesNuclear ProteinsProteasome Endopeptidase ComplexProto-Oncogene ProteinsProto-Oncogene Proteins c-mdm2Proto-Oncogene Proteins p21(ras)Receptors, EstrogenReceptors, Glucocorticoid

Identifiers

PMID12897156
PMCPMC166332
OpenAlexW2118578196

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.