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)

Aberrant retinoid signaling in human cancers is extending from the nucleus to the cytoplasm. Recently, we have demonstrated frequent epigenetic inactivation of a retinoic acid receptor (RAR), RARbeta2, in nasopharyngeal carcinoma (NPC). To further explore targets contributing to aberrant retinoid signaling in NPC, the expression of cellular retinol-binding proteins (CRBPs), cellular retinoic acid-binding proteins (CRABPs), RARs, and retinoid X receptors (RXRs) was examined. Apart from RARbeta2, transcriptional silencing of two CRBPs, CRBPI and CRBPIV, was observed in NPC cell lines and xenografts. Hypermethylation of CRBPI and CRBPIV CpG islands was found to be closely correlated with the loss of expression. Treatment with the DNA methyltransferase inhibitor, 5-aza-2'-deoxycytidine, resulted in reexpression of CRBP1 and CRBPIV gene expression in NPC cell lines. Both CRBPI and CRBPIV hypermethylations were also observed in 43/48 (87.8%) and 26/48 (54.2%) primary NPC tumors, respectively. Here, we reported for the first time that CRBPIV was transcriptionally inactivated by promoter hypermethylation in human cancer. Simultaneous methylation of CRBPI, CRBPIV, and RARbeta2 was commonly found in NPC primary tumors. Our findings implied that epigenetic disruption of the CRBPs, CRBPI and CRBPIV, is important in NPC tumorigenesis and may contribute to the loss of retinoic acid responsiveness in cancer.
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PMID:Epigenetic silencing of cellular retinol-binding proteins in nasopharyngeal carcinoma. 1572 Aug 18

Vitamin A is essential for normal growth and development. Epidemiology and laboratory studies suggest that decreased vitamin A levels and defective metabolism/ action may contribute to the genesis of certain cancers. Based on this information, natural and synthetic derivatives of vitamin A (retinoids) have been used for chemoprevention of cancer. Retinoids have had some success in the chemoprevention of leukoplakia and in the decreased incidence of second primaries in head and neck cancer. There is little information on biomarkers that can be used to assess the efficacy of the chemopreventive activity of retinoids. The ability of retinoids to induce RARb has been consistently shown to correlate with the response of cells and tissues to retinoic acid, but few other biomarkers have been certified as indicators of retinoid activity. In light of the failure of the ATBC and CARET clinical intervention trials for chemoprevention of lung cancer, greater use of animal models for chemoprevention studies is necessary. The potential combination of phytochemicals that inhibit DNA methyltransferase activity with retinoids holds promise for more effective chemoprevention of retinoid-unresponsive premalignant lesions.
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PMID:Biomarker and animal models for assessment of retinoid efficacy in cancer chemoprevention. 1772 72

The hepatitis B virus-encoded X (HBx) protein coactivates transcription of a variety of viral and cellular genes and it is believed to play essential roles in viral replication and hepatocarcinogenesis. To examine the pleiotropic effects of HBx protein on host cell protein expression, we utilized 2-DE and MS analysis to compare and identify differentially expressed proteins between a stable HBx-transfected cell line (HepG2-HBx), constitutively expressing HBx, and vector control cells. Of the 60 spots identified as differentially expressed (+/- over 2-fold, p < 0.05) between the two cell lines, 54 spots were positively identified by MS/MS analysis. Several recent studies suggested that HBx was involved in regional hypermethylation of tumor suppressor genes and global hypomethylation of satellite 2 repeats during hepatocarcinogenesis; however, no specific gene has been reported as hypomethylated by HBx. Promoter methylation analysis was examined for those protein spots showing significant alterations, and our results revealed that specific genes, such as aldehyde dehydrogenase 1 (ALDH1), can be hypomethylated by HBx, and two calcium ion-binding proteins, S100A6 and S100A4, were hypermethylated by HBx and could be re-expressed by AZA (DNA methylase inhibitor) treatment. Moreover, via cluster and pathway analysis, we proposed a hypothetical model for the HBx regulatory circuit involving aberrant methylation of retinol metabolism-related genes and calcium homeostasis-related genes. In summary, we profiled proteome alterations between HepG2-HBx and control cells, and found that HBx not only induces regional hypermethylation but also specific hypomethylation of host cell genes.
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PMID:Proteomic profiling identifies aberrant epigenetic modifications induced by hepatitis B virus X protein. 1911 5