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)
Down-regulation of
Cx43
expression had been shown to occur in nasopharyngeal carcinoma cells. The present study was undertaken to estimate if methylation of the promoter region in
Cx43
gene was responsible for the repression of
Cx43
expression in the CNE-1 nasopharyngeal carcinoma cells. Calcein transfer and lucifer yellow transfer were detected to evaluate gap junction intercellular communication (GJIC) in CNE-1 cells. It was found that the control CNE-1 cells showed no fluorescent dye transfer. After treatment with
DNA methyltransferase
inhibitor 5-aza-CdR, fluorescent dye transfer between cells became obvious. RT-PCR and Western blot were performed to determine the expression of
Cx43
gene. The control CNE-1 cells showed a low expression level of
Cx43
, whereas 5-aza-CdR-treated CNE-1 cells showed an enhanced level of
Cx43
expression. Methylation-sensitive restriction enzyme and PCR analysis showed that the methylation of the
Cx43
gene promoter region occurred in CNE-1 cells. In addition, treatment with 5-aza-CdR inhibited the growth (including anchorage-independent growth) of CNE-1 cells, and resulted in an accumulation of cells in G0/G1 phase. These results indicate the promoter methylation as an important role in inactivation of
Cx43
in CNE-1 cells.
...
PMID:Downregulation of connexin 43 in nasopharyngeal carcinoma cells is related to promoter methylation. 1730 7
To identify epigenetically silenced cancer-related genes and to determine molecular effects of 5-aza-2'-deoxycytidine (Aza-dC) and/or trichostatin A (TSA) in multiple myeloma (MM), we analyzed global changes in gene expression profiles of three MM cell lines by microarray analysis. We identified up-regulation of several genes whose epigenetic silencing in MM is well known. However, much more importantly, we identified a large number of epigenetically inactivated cancer-related genes that are involved in various physiologic processes and whose epigenetic regulation in MM was unknown thus far. In addition, drug treatment of MM cell lines resulted in down-regulation of several MM proliferation-associated factors (i.e., MAF, CCND1/2, MYC, FGFR3, MMSET). Ten Aza-dC and/or TSA up-regulated genes (CPEB1, CD9,
GJA1
, BCL7c, GADD45G, AKAP12, TFPI2, CCNA1, SPARC, and BNIP3) were selected for methylation analysis in six MM cell lines, 24 samples from patients with monoclonal gammopathy of undetermined significance (MGUS), and 111 samples from patients with MM. Methylation frequencies of these genes ranged between 0% and 17% in MGUS samples and between 5% and 50% in MM samples. Interestingly, methylation of SPARC and BNIP3 was statistically significantly associated with a poor overall survival of MM patients (P = 0.003 and P = 0.017, respectively). Moreover, SPARC methylation was associated with loss of SPARC protein expression by immunostaining in a subset of MM patients. In conclusion, we identified new targets for aberrant methylation in monoclonal gammopathies, and our results suggest that
DNA methyltransferase
and histone deacetylase inhibition might play an important role in the future treatment of patients with MM.
...
PMID:Genome-wide transcriptional response to 5-aza-2'-deoxycytidine and trichostatin a in multiple myeloma cells. 1817 95
