Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.1.1.37 (
DNA methyltransferase
)
4,983
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Expression of
cyclin D2
is absent in 30-70% of gastric cancers. We investigated the role of promoter hypermethylation in the transcriptional silencing of
cyclin D2
in five gastric cell lines and 47 primary gastric carcinomas. CpG island methylation status of the
cyclin D2
gene was studied by methylation-specific polymerase chain reaction and bisulphite sequencing. RNA and protein expression was analysed by reverse transcription-PCR and Western blot, respectively. Dense methylation of
cyclin D2
was detected in three cell lines (KATOIII, AGS and NCI-N87), which also lacked
cyclin D2
mRNA and protein expression. Bisulphite DNA sequencing revealed that loss of
cyclin D2
expression was closely associated with the density of methylation in the promoter region. Treatment with
DNA methyltransferase
inhibitor, 5-aza-2'-deoxycytidine, restored the
cyclin D2
expression level in methylated gastric cells. Among the 47 primary gastric cancers,
cyclin D2
hypermethylation was detected in 23 (48.9%) cases. None of the 23 normal gastric biopsies from noncancer patients showed hypermethylation. Hypermethylation was associated with loss of mRNA (P&<0.001) and protein (P=0.006) expressions. Our study showed that
cyclin D2
hypermethylation is associated with loss of
cyclin D2
expression in a subset of gastric cancers, which may suggest an alternative gastric carcinogenesis pathway in the absence of
cyclin D2
expression.
...
PMID:Absence of cyclin D2 expression is associated with promoter hypermethylation in gastric cancer. 1277 22
Arsenic trioxide (As
2
O
3
) has been used clinically as an anti-tumor agent. Its mechanisms are mostly considered to be the induction of apoptosis and cell cycle arrest. However, the detailed molecular mechanisms of its anti-cancer action through cell cycle arrest are poorly known. Furthermore, As
2
O
3
has been shown to be a potential DNA methylation inhibitor, inducing DNA hypomethylation. We hypothesize that As
2
O
3
may affect the expression of cell cycle regulatory genes by interfering with DNA methylation patterns. To explore this, we examined promoter methylation status of 24 cell cycle genes in breast cancer cell lines and in a normal breast tissue sample by methylation-specific polymerase chain reaction and/or restriction enzyme-based methods. Gene expression level and cell cycle distribution were quantified by real-time polymerase chain reaction and flow cytometric analyses, respectively. Our methylation analysis indicates that only promoters of RBL1 (p107), RASSF1A, and
cyclin D2
were aberrantly methylated in studied breast cancer cell lines. As
2
O
3
induced CpG island demethylation in promoter regions of these genes and restores their expression correlated with
DNA methyltransferase
inhibition. As
2
O
3
also induced alterations in messenger RNA expression of several cell cycle-related genes independent of demethylation. Flow cytometric analysis revealed that the cell cycle arrest induced by As
2
O
3
varied depending on cell lines, MCF-7 at G1 phase and both MDA-MB-231 and MDA-MB-468 cells at G2/M phase. These changes at transcriptional level of the cell cycle genes by the molecular mechanisms dependent and independent of demethylation are likely to represent the mechanisms of cell cycle redistribution in breast cancer cells, in response to As
2
O
3
treatment.
...
PMID:Demethylation and alterations in the expression level of the cell cycle-related genes as possible mechanisms in arsenic trioxide-induced cell cycle arrest in human breast cancer cells. 2821 39
