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)

Effective therapies for primary brain tumors continue to be elusive. Successful adjuvant therapies for CNS tumors will require a better understanding of their basic biology. Hepatocyte growth factor activator inhibitor type-2/placental bikunin (HAI-2/PB) is a serine proteinase inhibitor that has a broad inhibitory spectra against various serine proteinases. HAI-2/PB has anti-invasive effects thought to be mediated primarily by the inhibitory activity against serine proteinase-dependent matrix degradation. It has been previously demonstrated that the expression of HAI-2/PB is inversely related to degree of malignancy and possibly involved in the progression and invasion of human gliomas. Aberrant methylation patterns are an early change in glioma tumorigenesis, earlier than genetic changes. Methylation within 5' regulatory CpG islands by DNA methyltransferase is one of the most common epigenetic modifications. 5-Aza-2'-deoxycytidine (azacytidine) inhibits DNA methyltransferase and has been used in vitro to induce the expression of genes silenced by methylation. We have utilized azacytidine treatment and a micro-array system to investigate methylation influenced gene expression across several tumor cell lines of different lineage (brain, breast, prostate, liver). Using this system we have demonstrated that the expression of HAI-2/PB is under methylation control to a variable extent in glioma cell lines, in comparison to the other tested cell lines. Because the expression of HAI-2/B is inversely related to glioma invasiveness and degree of malignancy, this finding may provide insight into glioma initiation and progression as well as potentially providing new therapeutic targets.
 ...
PMID:Differential expression of bikunin (HAI-2/PB), a proposed mediator of glioma invasion, by demethylation treatment. 1455 97

EGCG (epigallocatechin gallate), the major catechin found in green tea, has been shown to inhibit proliferation and induce apoptosis in many tumors. EGCG can inhibit DNMT (DNA methyltransferase) activity, and cause CpG demethylation and reactivation of methylation-silenced genes. Tissue factor pathway inhibitor-2 (TFPI-2), a member of the Kunitz-type serine proteinase inhibitor family, is inversely related to an increasing degree of malignancy. Our previous study showed that the expression of TFPI-2 and invasiveness of renal cell carcinoma had a negative correlation. Overexpression of TFPI-2 may induce tumor cell apoptosis in renal cell carcinoma. Lower expression of TFPI-2 in renal cell carcinoma was partly due to hypermethylation of the gene promoter. Herein, using MTT and flow cytometry, we demonstrated that EGCG can inhibit growth and induces apoptosis in renal cell carcinoma cell line 786-0. In addition, Western blotting and real-time RT-PCR showed that EGCG can upregulate expression of TFPI-2. Before and after EGCG treatment, real-time methylation specific PCR could not detect methylation status of TFPI-2 gene promoter in cell line 786-0. In vivo invasiveness and metastasis test did not indicate any significant differences between control and treatment group. Our results suggest that EGCG inhibits growth and induces apoptosis in renal cell carcinoma through TFPI-2 overexpression. This is the first report showing that EGCG is likely to be an effective agent for renal cell carcinoma.
 ...
PMID:EGCG inhibits growth and induces apoptosis in renal cell carcinoma through TFPI-2 overexpression. 1921 21