In mammalians, demethylation of specific promoter regions often correlates with gene activation; inversely, dense methylation of CpG islands leads to gene silencing, probably mediated by methyl-CpG binding proteins. In cell lines and cancers, inhibition of tissue-specific genes and tumor suppressor genes expression seems to be related to such hypermethylation. The 5' end of the breast cancer pr...

Loss of heterozygosity on 9p21, where thepl6/CDKN2 tumor suppres sor and the pJ5INK4Bcell cycle regulator genes are located, is a common genetic alteration in bladder cancer. However, it has been difficult to demonstrate homozygous deletions and intragenic mutations in either of these two genes in primary transitional cell carcinomas (TCC) of the bladder. Similarly, colon cancer-derived cell li...

transcription start site and silencing of the heterochromatinization of the MGMT (MGMT) CpG island is associated with O6-methylguanine DNA methyltransferase Methylation of discrete regions of the

More than 50% of mammalian genes are associated with CpG islands and thus they serve as a good gene marker. We have devised a simple method to scan large pieces of native or cloned genomic DNA for CpG islands. The method is based on the presence of multiple Hpa II and Hha I sites in CpG islands, at a frequency 30 times higher than in the rest of the genome. The steps include complete digestion ...

In contrast to other globin genes, the human and rabbit alpha-globin genes are expressed in transfected erythroid and nonerythroid cells in the absence of an enhancer. This enhancer-independent expression of the alpha-globin gene requires extensive sequences not only from the 5' flanking sequence but also from the intragenic region. However, the features of these internal sequences that are res...

PURPOSE Gastrokine 1 plays an important role in gastric mucosal defense. Additionally, the Gastrokine 1-miR-185-DNMT1 axis has been shown to suppress gastric carcinogenesis through regulation of epigenetic alteration. Here, we investigated the effects of Gastrokine 1 on DNA methylation and gastritis. MATERIALS AND METHODS Expression of Gastrokine 1, DNMT1, EZH2, and c-Myc proteins, and the pr...

Previous studies suggested that the I III i (fragile histidine triad) gene on 3pl4.2 might be involved in the development of esophageal squamous cell carcinomas, but the mechanisms for inactivating the gene have not been fully revealed. In the present study, we examined aberrations of the I III! gene in 23 esophageal squamous cell carcinoma cell lines and 35 primary tumors. We detected aberrant...

Aberrant promoter methylation is an important mechanism for gene silencing. Inflammation-related reactive oxygens contribute to this CpG island methylation. The nuclear factor-erythroid 2-related factor 2 gene (Nrf2) is known to regulate the expression of detoxifying and antioxidant genes. We investigated the relationship between promoter polymorphisms of Nrf2 gene and the CpG island methylatio...

Cyclooxygenases (COXs) are key enzymes that convert arachidonic acid to prostaglandins. Overexpression of one of the COX isozymes, COX2, has been shown to play an important role in colorectal cancer progression. Recently, however, low expression of COX2 has been reported in a subset of colorectal and gastric cancers. Aberrant CpG island methylation and associated transcriptional silencing are c...