ArticleJournal of neuro-oncology2014
Epigenetic repression of the dopamine receptor D4 in pediatric tumors of the central nervous system.
Article in Journal of neuro-oncology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 24 citations in OpenAlex.
- Epigenetic Regulation of Inflammation by Dopamine in Primary Human Macrophages.bioRxiv : the preprint server for biology · 2026Article
- Epigenetic regulation of inflammation by dopamine in primary human macrophages.Frontiers in immunology · 2026Article
- Association of DRD4 promoter-associated methylation with mild cognitive impairment in Han and Uygur populations.European journal of medical research · 2025Article
- DRD4 Interacts with TGF-β Receptors to Drive Colorectal Cancer Metastasis Independently of Dopamine Signaling Pathway.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Comparison of tumor and two types of paratumoral tissues highlighted epigenetic regulation of transcription during field cancerization in non-small cell lung cancer.BMC medical genomics · 2022Article
- Ferroptosis-related genes are potential prognostic molecular markers for patients with colorectal cancer.Clinical and experimental medicine · 2021Article
- Medulloblastoma epigenetics and the path to clinical innovation.Journal of neuro-oncology · 2020Review
- Dissecting Intra-Tumor Heterogeneity by the Analysis of Copy Number Variations in Single Cells: The Neuroblastoma Case Study.International journal of molecular sciences · 2019Article
- The Prospective Value of Dopamine Receptors on Bio-Behavior of Tumor.Journal of Cancer · 2019Review
- Detection of lower levels of SNAP25 using multiple microarray systems and its functional significance in medulloblastoma.International journal of molecular medicine · 2017Article
- Inhibition of Dopamine Receptor D4 Impedes Autophagic Flux, Proliferation, and Survival of Glioblastoma Stem Cells.Cancer cell · 2016Article
- The Role of H3K4me3 in Transcriptional Regulation Is Altered in Huntington's Disease.PloS one · 2015Article
- Roles of dopamine receptors and their antagonist thioridazine in hepatoma metastasis.OncoTargets and therapy · 2015Article
- Gene expression analyses of the spatio-temporal relationships of human medulloblastoma subgroups during early human neurogenesis.PloS one · 2014Article
Corrections and comments
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Authors and funding
13 authors at 9 institutions in 5 countries.
Funding
Abstract
Epigenetic alterations are common events in cancer. Using a genome wide methylation screen (Restriction Landmark Genomic Scanning-RLGS) we identified the gene for the dopamine receptor D4 (DRD4) as tumor-specific methylated. As DRD4 is involved in early brain development and may thus be involved in developmentally dependent tumors of the CNS in children epigenetic deregulation of DRD4 and its functional consequences were analyzed in vitro. CpG methylation of DRD4 was detected in 18/24 medulloblastomas, 23/29 ependymomas, 6/6 high-grade gliomas, 7/10 CNS PNET and 8/8 cell lines by qCOBRA and bisulfite sequencing. Real-time RT-PCR demonstrated a significantly inferior expression of DRD4 in primary tumors compared to cell lines and non-malignant control tissues. Epigenetic deregulation of DRD4 was analyzed in reexpression experiments and restoration of DRD4 was observed in medulloblastoma (MB) cells treated with 5-Aza-CdR. Reexpression was not accompanied by demethylation of the DRD4 promoter but by a significant decrease of H3K27me3 and of bound enhancer of zeste homologue 2 (EZH2). Knockdown of EZH2 demonstrated DRD4 as a direct target for inhibition by EZH2. Stimulation of reexpressed DRD4 resulted in an activation of ERK1/2. Our analyses thus disclose that DRD4 is epigenetically repressed in CNS tumors of childhood. DRD4 is a direct target of EZH2 in MB cell lines. EZH2 appears to dominate over aberrant DNA methylation in the epigenetic inhibition of DRD4, which eventually leads to inhibition of a DRD4-mediated stimulation of the ERK1/2 kinase pathway.
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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.