Evidence map›Paper›PMID 20062804›Full record

ArticlePloS one2010

Nrf2 expression is regulated by epigenetic mechanisms in prostate cancer of TRAMP mice.

Siwang Yu, Tin Oo Khor, Ka-Lung Cheung, Wenge Li, Tien-Yuan Wu, Ying Huang, Barbara A Foster, Yuet Wai Kan, Ah-Ng Kong

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 131 papers.

0numbers the graph read from it
0cells of the map it votes in
131citing papers in PubMed
7.6field-weighted citation impact, top 2% 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

131 citing papers in PubMed, 223 citations in OpenAlex.

  1. Trial
  2. Article
  3. Article
  4. Review
  5. Review
  6. NRF2 Dysregulation and Therapeutic Insights Across Chronic Kidney Diseases.International journal of molecular sciences · 2025
    Review
  7. Review
  8. Review
  9. Review
  10. Article
  11. Review
  12. The Role of NRF2 in Trinucleotide Repeat Expansion Disorders.Antioxidants (Basel, Switzerland) · 2024
    Review
  13. Review
  14. Transcription Factor NRF2 in Shaping Myeloid Cell Differentiation and Function.Advances in experimental medicine and biology · 2024
    Review
  15. Review
  16. Article
  17. Review
  18. Article
  19. Review
  20. Article

71 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

9 authors at 3 institutions in 1 country.

Siwang YuDepartment of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey, United States of America.
Tin Oo Khor
Ka-Lung Cheung
Wenge Li
Tien-Yuan Wu
Ying Huang
Barbara A Foster
Yuet Wai Kan
Ah-Ng Kong
Rutgers, The State University of New Jersey · USRoswell Park Comprehensive Cancer Center · USUniversity of California, San Francisco · US

Funding

Translational Research Support CoreP30ES005022 · NIEHS · UNIV OF MED/DENT NJ-R W JOHNSON MED SCH · PI ROBERT John LAUMBACH · 1988 to 2026
$47.4M
Epigenetic modifications by dietary PEITC in prostate cancerR01CA118947 · NCI · RUTGERS, THE STATE UNIV OF N.J. · PI KONG, AH-NG TONY · 2006 to 2015
$2.8M
NCI NIH HHS R01 CA118947NCI NIH HHS R01-CA118947NIEHS NIH HHS P30 ES005022PHS HHS R01-094828
6 · The paper itself

Abstract

Nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) is a transcription factor which regulates the expression of many cytoprotective genes. In the present study, we found that the expression of Nrf2 was suppressed in prostate tumor of the Transgenic Adenocarcinoma of Mouse Prostate (TRAMP) mice. Similarly, the expression of Nrf2 and the induction of NQO1 were also substantially suppressed in tumorigenic TRAMP C1 cells but not in non-tumorigenic TRAMP C3 cells. Examination of the promoter region of the mouse Nrf2 gene identified a CpG island, which was methylated at specific CpG sites in prostate TRAMP tumor and in TRAMP C1 cells but not in normal prostate or TRAMP C3 cells, as shown by bisulfite genomic sequencing. Reporter assays indicated that methylation of these CpG sites dramatically inhibited the transcriptional activity of the Nrf2 promoter. Chromatin immunopreceipitation (ChIP) assays revealed increased binding of the methyl-CpG-binding protein 2 (MBD2) and trimethyl-histone H3 (Lys9) proteins to these CpG sites in the TRAMP C1 cells as compared to TRAMP C3 cells. In contrast, the binding of RNA Pol II and acetylated histone H3 to the Nrf2 promoter was decreased. Furthermore, treatment of TRAMP C1 cells with DNA methyltransferase (DNMT) inhibitor 5-aza-2'-deoxycytidine (5-aza) and histone deacetylase (HDAC) inhibitor trichostatin A (TSA) restored the expression of Nrf2 as well as the induction of NQO1 in TRAMP C1 cells. Taken together, these results indicate that the expression of Nrf2 is suppressed epigenetically by promoter methylation associated with MBD2 and histone modifications in the prostate tumor of TRAMP mice. Our present findings reveal a novel mechanism by which Nrf2 expression is suppressed in TRAMP prostate tumor, shed new light on the role of Nrf2 in carcinogenesis and provide potential new directions for the detection and prevention of prostate cancer.

Indexed as

Epigenesis, GeneticAnimalsAzacitidineCpG IslandsDNA MethylationMaleMiceNF-E2-Related Factor 2Prostatic NeoplasmsReceptors, Tumor Necrosis Factor, Member 25Transcription, GeneticTrichosanthinAzacitidineNfe2l2 protein, mouseNF-E2-Related Factor 2Receptors, Tumor Necrosis Factor, Member 25Tnfrsf25 protein, mouseTrichosanthin

Identifiers

PMID20062804
PMCPMC2799519
OpenAlexW2078348655

What OpenQuestion holds

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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.