Evidence map›Paper›PMID 22235307›Full record

ArticlePloS one2012

Distinct roles for aryl hydrocarbon receptor nuclear translocator and ah receptor in estrogen-mediated signaling in human cancer cell lines.

Mark P Labrecque, Mandeep K Takhar, Brett D Hollingshead, Gratien G Prefontaine, Gary H Perdew, Timothy V Beischlag

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed, 1 pooled it
5.9field-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

16 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Article
  5. The GenusFrontiers in pharmacology · 2021
    Review
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Coactivator recruitment of AhR/ARNT1.International journal of molecular sciences · 2014
    Review
  12. Article
  13. Article
  14. Role of the aryl hydrocarbon receptor in carcinogenesis and potential as a drug target.Toxicological sciences : an official journal of the Society of Toxicology · 2013
    Review
  15. Smoke carcinogens cause bone loss through the aryl hydrocarbon receptor and induction of Cyp1 enzymes.Proceedings of the National Academy of Sciences of the United States of America · 2013
    Article
  16. Emerging targets in lipid-based therapy.Biochemical pharmacology · 2013
    Review
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

6 authors at 2 institutions in 2 countries.

Mark P LabrecqueThe Faculty of Health Sciences, Simon Fraser University, Burnaby, Canada.
Mandeep K Takhar
Brett D Hollingshead
Gratien G Prefontaine
Gary H Perdew
Timothy V Beischlag
Simon Fraser University · CAPennsylvania State University · US

Funding

REGULATION OF THE AH RECEPTORR01ES004869 · NIEHS · PURDUE UNIVERSITY WEST LAFAYETTE · PI PERDEW, GARY H. · 1994 to 2017
$5.3M
CIHR ES04869NIEHS NIH HHS R01 ES004869
6 · The paper itself

Abstract

The activated AHR/ARNT complex (AHRC) regulates the expression of target genes upon exposure to environmental contaminants such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Importantly, evidence has shown that TCDD represses estrogen receptor (ER) target gene activation through the AHRC. Our data indicates that AHR and ARNT act independently from each other at non-dioxin response element sites. Therefore, we sought to determine the specific functions of AHR and ARNT in estrogen-dependent signaling in human MCF7 breast cancer and human ECC-1 endometrial carcinoma cells. Knockdown of AHR with siRNA abrogates dioxin-inducible repression of estrogen-dependent gene transcription. Intriguingly, knockdown of ARNT does not effect TCDD-mediated repression of estrogen-regulated transcription, suggesting that AHR represses ER function independently of ARNT. This theory is supported by the ability of the selective AHR modulator 3',4'-dimethoxy-α-naphthoflavone (DiMNF) to repress estrogen-inducible transcription. Furthermore, basal and estrogen-activated transcription of the genes encoding cathepsin-D and pS2 are down-regulated in MCF7 cells but up-regulated in ECC-1 cells in response to loss of ARNT. These responses are mirrored at the protein level with cathepsin-D. Furthermore, knock-down of ARNT led to opposite but corresponding changes in estrogen-stimulated proliferation in both MCF7 and ECC-1 cells. We have obtained experimental evidence demonstrating a dioxin-dependent repressor function for AHR and a dioxin-independent co-activator/co-repressor function for ARNT in estrogen signalling. These results provide us with further insight into the mechanisms of transcription factor crosstalk and putative therapeutic targets in estrogen-positive cancers.

Indexed as

Signal TransductionAryl Hydrocarbon Receptor Nuclear TranslocatorCell Line, TumorCell ProliferationEstrogen Receptor alphaEstrogensGene Knockdown TechniquesHumansPhenotypePolychlorinated DibenzodioxinsReceptors, Aryl HydrocarbonRNA, MessengerTranscription, GeneticAryl Hydrocarbon Receptor Nuclear TranslocatorEstrogen Receptor alphaEstrogensPolychlorinated DibenzodioxinsReceptors, Aryl HydrocarbonRNA, Messenger

Identifiers

PMID22235307
PMCPMC3250444
OpenAlexW2085658235

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.