Evidence map›Paper›PMID 16954373›Full record

ArticleMolecular and cellular biology2006

Aberrant promoter methylation of the ABCG2 gene in renal carcinoma.

Kenneth K W To, Z Zhan, Susan E Bates

Open access · greenAbstract read
In one paragraph

Article in Molecular and cellular biology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed
3.4field-weighted citation impact, top 8% 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

54 citing papers in PubMed, 119 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Review
  5. Review
  6. Review
  7. International journal of molecular sciences · 2023
    Article
  8. Review
  9. Multidrug efflux transporter ABCG2: expression and regulation.Cellular and molecular life sciences : CMLS · 2021
    Review
  10. Review
  11. Oncometabolites in renal cancer.Nature reviews. Nephrology · 2020
    Review
  12. Transcription factor-mediated regulation of the BCRP/Expert opinion on drug metabolism & toxicology · 2020
    Review
  13. Article
  14. Review
  15. Germline variants in cancer therapy.Cancer drug resistance (Alhambra, Calif.) · 2019
    Review
  16. The Role of DNA Methylation in Renal Cell Carcinoma.Molecular diagnosis & therapy · 2018
    Review
  17. Review
  18. Review
  19. Review
  20. 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

3 authors at 3 institutions in 1 country.

Kenneth K W ToExperimental Therapeutics Section, Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA. tok@mail.nih.gov
Z Zhan
Susan E Bates
Center for Cancer Research · USNational Cancer Institute · USNational Institutes of Health · US

Funding

Investigation of the ABC Half-Transporter ABCG2ZIABC010622 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI BATES, SUSAN · 2009 to 2015
$2.3M
Investigation of the ABC Half-Transporter ABCG2Z01BC010622 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI BATES, SUSAN · 2004 to 2008
$1.5M
Intramural NIH HHS
6 · The paper itself

Abstract

ABCG2 is a ubiquitous ATP-binding cassette transmembrane protein that is important in clinical drug resistance. Little is known about the mechanism(s) regulating the expression of ABCG2. We hypothesized that DNA methylation could play a role in the epigenetic regulation of ABCG2 gene expression. The promoter methylation status of three renal carcinoma cell lines was assessed with restriction enzyme digestion-coupled PCR and bisulfite genomic sequencing. Both UOK121 and UOK143, with known methylation of the VHL promoter, showed induction of ABCG2 expression after 5-aza-2'-deoxycytidine (5-aza-dC) treatment, suggesting that aberrant methylation of the ABCG2 gene was associated with gene silencing. In vitro methylation of the ABCG2 promoter-driven luciferase reporter vector resulted in a significant inhibition of transcription. Our data suggested that the ABCG2 gene is regulated coordinately at both histone and DNA levels. A chromatin immunoprecipitation assay demonstrated that the methylated promoter in UOK121 and UOK143, but not the unmethylated one in UOK181, is associated with the methyl CpG binding domain proteins (MBDs), MBD2 and MeCP2. Histone deacetylase 1 and a corepressor, mSin3A, were identified binding to the promoter region containing the CpG island, thereby suppressing ABCG2 transcription. Reactivation of ABCG2 was achieved by treatment with 5-aza-dC, a demethylating agent, concomitant with the release of MBDs from the promoter. Furthermore, the association of methylated lysine 9 on histone H3, a hallmark of promoter methylation, with the promoter was reduced following 5-aza-dC treatment. These data suggest that DNA methylation-dependent formation of a repressor complex in the CpG island contributes to inactivation of ABCG2.

Indexed as

Promoter Regions, GeneticTranscription, GeneticATP-Binding Cassette TransportersATP Binding Cassette Transporter, Subfamily G, Member 2AzacitidineBase SequenceCarcinoma, Renal CellCell Line, TumorCpG IslandsDNA (Cytosine-5-)-Methyltransferase 1DNA (Cytosine-5-)-MethyltransferasesDNA MethylationDNA Methyltransferase 3AEpigenesis, GeneticHistonesHumansABCG2 protein, humanATP-Binding Cassette TransportersATP Binding Cassette Transporter, Subfamily G, Member 2AzacitidineDNA (Cytosine-5-)-Methyltransferase 1DNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3ADNMT3A protein, humanHistonesLysineNeoplasm ProteinsVHL protein, humanVon Hippel-Lindau Tumor Suppressor Protein

Identifiers

PMID16954373
PMCPMC1636795
OpenAlexW2002795755

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.