Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
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Target Concepts:
Gene/Protein
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Query: EC:2.1.1.37 (
DNA methyltransferase
)
4,983
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Promoter hypermethylation has become apparent as a common mechanism of gene silencing in cancer. Based on our published microarray expression data, we noticed a prominent downregulation of
ID4
in gastric adenocarcinoma. The dense 5' CpG island covering the previously mapped upstream promoter of
ID4
has prompted us to relate its downregulation to promoter hypermethylation. ID proteins are distinct members in the helix-loop-helix family of transcriptional regulators, which modulate various key developmental processes. Emerging data have suggested the involvement of ID genes in tumorigenesis. In this study using bisulfite genomic sequencing, we have found hypermethylation of
ID4
promoter in most gastric cancer cell lines and 30% of primary tumors. This correlated with decreased level of
ID4
expression. Restoration of
ID4
expression in various gastric cancer cell lines was achieved by treatment with the
DNA methyltransferase
inhibitor 5-aza-2'-deoxycytidine, which at times required the synergistic action of the histone deacetylase inhibitor trichostatin A, but not with trichostatin A alone. Re-expression was accompanied by the corresponding
ID4
promoter demethylation. Furthermore, we have found significant association of
ID4
promoter methylation with hMLH1 promoter methylation (P=0.008) and microsatellite instability (P=0.006). Overall, our results have shown that transcriptional silencing of
ID4
is related to the aberrant methylation of its promoter in gastric cancer. The significant association of
ID4
and hMLH1 promoter hypermethylation suggested that
ID4
may also be among the genes being targeted in the CpG island methylator phenotype tumorigenic pathway.
...
PMID:Downregulation of ID4 by promoter hypermethylation in gastric adenocarcinoma. 1453 43
Aberrant DNA methylation of 5'-CpG islands located within gene promoters has been identified as a mechanism for transcriptional inactivation of tumor suppressor genes. To ascertain the mechanism of gene promoter hypermethylation in cholangiocarcinoma (CC), we investigated promoter methylation status of the candidate genes
ID4
, DLC-1, and SFRP1 in 41 CCs, 19 adjacent nontumor tissues, and 15 normal liver tissues using methylation-specific PCR (MSP). The frequencies of DNA methylation were: 57.5% (23 of 40) for
ID4
, 14.3% (5 of 35) for DLC-1, and 63.4% (26 of 41) for SFRP1, respectively. In contrast, a low frequency of methylation was detected in nontumor tissues. In addition, hypermethylated status of these genes was detected in three kinds of CC cell lines. Moreover, the downregulated expression of these genes in these cells was restored by treatment with 5-aza-2'-deoxycytidine, a
DNA methyltransferase
inhibitor. Taken together, these results suggest that aberrant DNA methylation may contribute to the tumorigenesis of cholangiocarcinoma.
...
PMID:Aberrant promoter CpG islands methylation of tumor suppressor genes in cholangiocarcinoma. 1877 59
