RGD Reference Report - Evidence for estrogenic contamination of the MAPK inhibitor PD98059. - Rat Genome Database

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Evidence for estrogenic contamination of the MAPK inhibitor PD98059.

Authors: Long, X  Gize, EA  Nephew, K  Bigsby, RM 
Citation: Long X, etal., Endocrinology 2001 Dec;142(12):5390-3.
RGD ID: 727330
Pubmed: PMID:11713241   (View Abstract at PubMed)
DOI: DOI:10.1210/endo.142.12.8649   (Journal Full-text)

PD98059 blocks phosphorylation and activation of MAPK proteins, ERK1 and ERK2. In the course of examining the effect of PD98059 on estrogen-induced transcription of reporter genes in a human breast cancer cell line and in yeast, we found that two of four different batches of PD98059 produced estrogenic effects in a dose-dependent manner. In a competitive binding assay, these preparations of PD98059 displaced radiolabeled estradiol from ER alpha. Furthermore, in the yeast assay, addition of a coactivator protein, AIB1, enhanced the transcriptional effect of PD98059, indicating that it induces receptor-coactivator interactions. Although concentrations of PD98059 required to activate ER alpha in these experimental systems are 10(4)- to 10(5) higher than the concentration of estradiol required to do the same, the concentrations required to block MAPK activation are well above those which would produce maximal estrogenic effects. Thus, when PD98059 is used in estrogen-responsive cells, contaminating estrogenic activity may confound interpretation of experimental results.




Molecular Function

  
Object Symbol
Species
Term
Qualifier
Evidence
With
Notes
Source
Original Reference(s)
Esr1Ratestrogen binding  IDA  RGD 

RGD Manual Annotations


  
Object Symbol
Species
Term
Qualifier
Evidence
With
Notes
Source
Original Reference(s)
NCOA3Humanestrogen signaling pathway   ISONcoa3 (Rattus norvegicus) RGD 
Ncoa3Ratestrogen signaling pathway   IDA  RGD 
Ncoa3Mouseestrogen signaling pathway   ISONcoa3 (Rattus norvegicus) RGD 

Genes (Rattus norvegicus)
Esr1  (estrogen receptor 1) Ncoa3  (nuclear receptor coactivator 3)

Genes (Mus musculus)
Ncoa3  (nuclear receptor coactivator 3)

Genes (Homo sapiens)
NCOA3  (nuclear receptor coactivator 3)