Evidence map›Paper›PMID 24639079›Full record

ArticleCarcinogenesis2014

Modulation of aryl hydrocarbon receptor (AHR)-dependent signaling by peroxisome proliferator-activated receptor β/δ (PPARβ/δ) in keratinocytes.

Michael G Borland, Prasad Krishnan, Christina Lee, Prajakta P Albrecht, Weiwei Shan, Moses T Bility, Craig B Marcus, Jyh M Lin, Shantu Amin, Frank J Gonzalez and 2 more

Open access · bronzeAbstract read
In one paragraph

Article in Carcinogenesis, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.7field-weighted citation impact, top 16% 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

14 citing papers in PubMed, 30 citations in OpenAlex.

  1. Review
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  9. HJournal of experimental & clinical cancer research : CR · 2019
    Article
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  13. Retinoid-xenobiotic interactions: the Ying and the Yang.Hepatobiliary surgery and nutrition · 2015
    Review
  14. Article
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

12 authors at 4 institutions in 1 country.

Michael G BorlandDepartment of Veterinary and Biomedical Sciences and the Center of Molecular Toxicology and Carcinogenesis and The Graduate Program in Biochemistry, Microbiology, and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USA.
Prasad KrishnanDepartment of Veterinary and Biomedical Sciences and the Center of Molecular Toxicology and Carcinogenesis and.
Christina LeeDepartment of Veterinary and Biomedical Sciences and the Center of Molecular Toxicology and Carcinogenesis and.
Prajakta P AlbrechtDepartment of Veterinary and Biomedical Sciences and the Center of Molecular Toxicology and Carcinogenesis and.
Weiwei ShanDepartment of Veterinary and Biomedical Sciences and the Center of Molecular Toxicology and Carcinogenesis and.
Moses T BilityDepartment of Veterinary and Biomedical Sciences and the Center of Molecular Toxicology and Carcinogenesis and.
Craig B MarcusDepartment of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR 97331, USA.
Jyh M LinDepartment of Pharmacology, Penn State Cancer Institute, The Pennsylvania State University, Milton S. Hershey Medical Center, Hershey, PA 17033, USA and.
Shantu AminDepartment of Pharmacology, Penn State Cancer Institute, The Pennsylvania State University, Milton S. Hershey Medical Center, Hershey, PA 17033, USA and.
Frank J GonzalezLaboratory of Metabolism, National Cancer Institute, Bethesda, MD 20892, USA.
Gary H PerdewDepartment of Veterinary and Biomedical Sciences and the Center of Molecular Toxicology and Carcinogenesis and The Graduate Program in Biochemistry, Microbiology, and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USA.
Jeffrey M PetersDepartment of Veterinary and Biomedical Sciences and the Center of Molecular Toxicology and Carcinogenesis and The Graduate Program in Biochemistry, Microbiology, and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USA, jmp21@psu.edu.
Pennsylvania State University · USPenn State Milton S. Hershey Medical Center · USNational Cancer Institute · USOregon State University · US

Funding

Xenobiotic receptorsZIABC005562 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI GONZALEZ, FRANK J · 2009 to 2025
$26.9M
Xenobiotic ReceptorsZIABC005708 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI GONZALEZ, FRANK J · 2009 to 2025
$16.4M
REGULATION OF THE AH RECEPTORR01ES004869 · NIEHS · PURDUE UNIVERSITY WEST LAFAYETTE · PI PERDEW, GARY H. · 1994 to 2017
$5.3M
Modulation of skin cancer by PPARBeta/deltaR01CA124533 · NCI · PENNSYLVANIA STATE UNIVERSITY, THE · PI PETERS, JEFFREY M · 2007 to 2017
$2.4M
Selective Ah Receptor Ligands Repress Acute-Phase ResponseR01ES019964 · NIEHS · PENNSYLVANIA STATE UNIVERSITY, THE · PI PERDEW, GARY H. · 2012 to 2016
$2.0M
Transcriptional regulation of polycyclic aromatic hydrocarbon metabolismR01CA141029 · NCI · PENNSYLVANIA STATE UNIVERSITY, THE · PI PETERS, JEFFREY M · 2010 to 2013
$1.1M
Modulation of AhR-dependent signaling by PPARb/dR01CA126826 · NCI · PENNSYLVANIA STATE UNIVERSITY, THE · PI PETERS, JEFFREY M · 2009 to 2010
$594k
BIOCHEMICAL CHARACTERIZATION OF THE AH RECEPTORR29ES004869 · NIEHS · PURDUE UNIVERSITY WEST LAFAYETTE · PI PERDEW, GARY H · 1989 to 1993
–
NCI NIH HHS CA124533NCI NIH HHS CA141029NCI NIH HHS R01 CA124533NCI NIH HHS R01 CA126826NCI NIH HHS R01 CA141029NIEHS NIH HHS ES004869NIEHS NIH HHS ES019964NIEHS NIH HHS R01 ES004869NIEHS NIH HHS R01 ES019964
6 · The paper itself

Abstract

Whether peroxisome proliferator-activated receptor β/δ (PPARβ/δ) reduces skin tumorigenesis by altering aryl hydrocarbon receptor (AHR)-dependent activities was examined. Polycyclic aromatic hydrocarbons (PAH) increased expression of cytochrome P4501A1 (CYP1A1), CYP1B1 and phase II xenobiotic metabolizing enzymes in wild-type skin and keratinocytes. Surprisingly, this effect was not found in Pparβ/δ-null skin and keratinocytes. Pparβ/δ-null keratinocytes exhibited decreased AHR occupancy and histone acetylation on the Cyp1a1 promoter in response to a PAH compared with wild-type keratinocytes. Bisulfite sequencing of the Cyp1a1 promoter and studies using a DNA methylation inhibitor suggest that PPARβ/δ promotes demethylation of the Cyp1a1 promoter. Experiments with human HaCaT keratinocytes stably expressing shRNA against PPARβ/δ also support this conclusion. Consistent with the lower AHR-dependent activities in Pparβ/δ-null mice compared with wild-type mice, 7,12-dimethylbenz[a]anthracene (DMBA)-induced skin tumorigenesis was inhibited in Pparβ/δ-null mice compared with wild-type. Results from these studies demonstrate that PPARβ/δ is required to mediate complete carcinogenesis by DMBA. The mechanisms underlying this PPARβ/δ-dependent reduction of AHR signaling by PAH are not due to alterations in the expression of AHR auxiliary proteins, ligand binding or AHR nuclear translocation between genotypes, but are likely influenced by PPARβ/δ-dependent demethylation of AHR target gene promoters including Cyp1a1 that reduces AHR accessibility as shown by reduced promoter occupancy. This PPARβ/δ/AHR crosstalk is unique to keratinocytes and conserved between mice and humans.

Indexed as

9,10-Dimethyl-1,2-benzanthraceneAnimalsBasic Helix-Loop-Helix ProteinsBlotting, WesternCarcinogensCells, CulturedCell Transformation, NeoplasticChromatin ImmunoprecipitationDermisFemaleFibroblastsHumansImmunoenzyme TechniquesKeratinocytesMiceMice, Knockout9,10-Dimethyl-1,2-benzanthraceneAhr protein, mouseBasic Helix-Loop-Helix ProteinsCarcinogensPPAR-betaPPAR deltaReceptors, Aryl HydrocarbonRNA, Messenger

Identifiers

PMID24639079
PMCPMC4076811
OpenAlexW2233839107

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.