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)

In the present study, we addressed the molecular mechanism of the downregulation of reversion-inducing-cysteine-rich protein with Kazal motifs (RECK), a critical tumor suppressor that can potently inhibit angiogenesis and metastasis, in non-small cell lung cancer and its clinical significance. The methylation status of the RECK gene promoter was studied by methylation-specific polymerase chain reaction. RECK mRNA and protein levels were investigated by reverse transcription-polymerase chain reaction and western blot analysis. Downregulation of RECK was observed in 60% of the 55 tumors analyzed. Using methylation-specific polymerase chain reaction analysis methylation of the RECK promoter was detected in 63.6% (35/55) of the tumor tissues. A strong correlation between downregulation and promoter methylation was found in these tumors (P = 0.000005). More importantly, downregulation of RECK significantly correlated with lymph node metastasis (P = 0.038). Mutation of codon 12 of the K-ras gene was detected in 25.5% (14/55) of lung tumor tissues. Statistical analysis indicated that K-ras mutation was linked with RECK promoter methylation (P = 0.047) and downregulation (P = 0.023). Promoter methylation was also detected in human lung cancer cell lines, and the DNA methyltransferase inhibitor 5'-azacytidine reversed the expression of RECK and reduced the invasive ability of these cell lines. Collectively, our results suggest that downregulation of the metastasis suppressor RECK is caused by promoter methylation in non-small cell lung cancer and is associated with K-ras mutation and lymph node metastasis.
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PMID:Downregulation of RECK by promoter methylation correlates with lymph node metastasis in non-small cell lung cancer. 1723 34

The objective of this study was to evaluate molecular markers involved in mammary tumorigenesis in a canine model that mimics many essential elements of human breast cancer. Thirty mammary gland tumors and control tissues obtained from female dogs were included in the study. We analyzed changes in the expression of markers of hormone and receptor status (estradiol, estrogen receptor; ER and HER-2/neu), hormone metabolism (CYP1A1 and CYP1B1), cell proliferation and survival [proliferating cell nuclear antigen (PCNA), glutathione S-transferase-P (GST-P), nuclear factor-kappaB (NF-kappaB-p50, NF-kappaB-p65), phosphorylated-inhibitor of kappaB-alpha (p-IkappaB-alpha) and IkappaB], apoptosis (Bcl-2, Bax, caspases, Apaf-1, cytochrome-C, and PARP), invasion [matrix metalloproteinases-2 and -9 (MMP-2, MMP-9), tissue inhibitor of matrix metalloproteinase-2 (TIMP-2), and reversion-inducing cysteine-rich protein with Kazal motifs (RECK)], angiogenesis [vascular endothelial growth factor (VEGF)], and epigenetics [DNA methyltransferase (Dnmt-1), histone deacetylase (HDAC-1)] by immunohistochemical localization and Western blot analysis and correlated these with histological grade. The present study provides evidence that increased expression of ER, HER-2/neu, estradiol, and its metabolizing enzymes, as well as proteins involved in cell proliferation, apoptosis evasion, invasion, and angiogenesis may confer a selective growth advantage to canine mammary tumors. To our knowledge this is the first report on the hallmark capabilities of canine mammary tumors, which lends credence to the view that the dog is a valuable model for human breast cancer studies.
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PMID:Evaluation of molecular markers in canine mammary tumors: correlation with histological grading. 2022 57

Reversion-inducing cysteine-rich protein with kazal motifs (RECK), a novel tumor suppressor gene that negatively regulates matrix metalloproteinases (MMPs), is expressed in various normal human tissues but downregulated in several types of human tumors. The molecular mechanism for this downregulation and its biological significance in salivary adenoid cystic carcinoma (SACC) are unclear. In the present study, we investigated the effects of a DNA methyltransferase (DNMT) inhibitor, 5-aza-2'deoxycytidine (5-aza-dC), on the methylation status of the RECK gene and tumor invasion in SACC cell lines. Methylation-specific PCR (MSP), Western blot analysis, and quantitative real-time PCR were used to investigate the methylation status of the RECK gene and expression of RECK mRNA and protein in SACC cell lines. The invasive ability of SACC cells was examined by the Transwell migration assay. Promoter methylation was only found in the ACC-M cell line. Treatment of ACC-M cells with 5-aza-dC partially reversed the hypermethylation status of the RECK gene and significantly enhanced the expression of mRNA and protein, and 5-aza-dC significantly suppressed ACC-M cell invasive ability. Our findings showed that 5-aza-dC inhibited cancer cell invasion through the reversal of RECK gene hypermethylation, which might be a promising chemotherapy approach in SACC treatment.
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PMID:Effects of 5-aza-2'deoxycytidine on RECK gene expression and tumor invasion in salivary adenoid cystic carcinoma. 2551 20