Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.1.1.37 (DNA methyltransferase)
 4,983 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Camptothecin (CPT) reversibly binds and stabilizes cleavable complexes formed between DNA and topoisomerase I (Top1), thereby activating many downstream signaling pathways. Although several pathways induced by CPT have been elucidated, there are additional proteins that represent targets of CPT pharmacological mechanisms and remain uncharacterized. Using two-dimensional electrophoresis analysis and matrix assisted laser desorption/ionization-time of flight (MALDI-TOF)-MS/MS identification, we investigated the hepatocellular carcinoma cell line SMMC-7721 for changes of protein expression following CPT treatment. Proteomic results showed that CPT treatment caused decreased expression of galectin-1 in SMMC-7721 cells. Quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) analysis confirmed mRNA expression changes in galectin-1. Protein expression levels of DNA methyltransferases (DNMTs) were downregulated in response to CPT. The DNMT inhibitor 5-aza-2'-deoxycytidine (DAC) sensitized SMMC-7721 cells to the cytotoxic effect of CPT. Our results indicate that inhibition of DNMT activity by CPT may play a role in CPT-induced cell proliferation inhibition and apoptosis.
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PMID:Camptothecin-induced cell proliferation inhibition and apoptosis enhanced by DNA methyltransferase inhibitor, 5-aza-2'-deoxycytidine. 1948 24

Human leukocyte antigen-G (HLA-G) is highly expressed in numerous solid tumor cell types and has important roles in protecting tumor cells from host immune recognition and destruction. DNA methylation modification, which may regulate gene expression, is aberrant in numerous tumor cell types. However, whether the high expression of HLA-G in tumor cells is induced by aberrant DNA methylation has remained elusive. In the present study, HLA-G, DNA methyltransferase (DNMT) and ten-eleven translocation (TET) expression, as well as the DNA methylation level of HLA-G, were assessed in the HBL-100 breast cell line and the MCF-7 breast cancer cell line. The influence of TET on the expression and DNA methylation levels of HLA-G in MCF-7 was assessed through treatment with the TET inhibitor dimethyloxallyl glycine (DMOG). The results indicated that HLA-G expression was significantly greater in MCF-7 than that in HBL-100 cells; however, the DNA methylation level of HLA-G was lower in MCF-7 than that in HBL-100 cells. Furthermore, in MCF-7 cells, DNMT1 and DNMT3a were expressed at lower levels and TET2 was expressed at higher levels than in HBL-100 cells. Treatment with DMOG significantly decreased HLA-G expression, while increasing the DNA methylation level of HLA-G in MCF-7. In conclusion, the results indicated that overexpression of HLA-G in MCF-7 cells was induced by DNA methylation modification. The lower DNMT1 and DNMT3a and higher TET2 expression levels may be responsible for the abnormal DNA methylation of HLA-G in MCF-7. Treatment with TET inhibitor prevented aberrant HLA-G expression and DNA methylation in MCF-7. The present study may provide potential targets for novel anti-cancer drugs.
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PMID:Role of gene promoter methylation regulated by TETs and DNMTs in the overexpression of HLA-G in MCF-7 cells. 3108 5