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Analyses The The Methylation Status Of Runx3 Gene In The In Gastric Carcinoma And Corresponding Non-neoplastic Gastric

Posted on:2008-06-24Degree:MasterType:Thesis
Country:ChinaCandidate:Z G WangFull Text:PDF
GTID:2144360212996267Subject:Surgery
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The RUNX3 gene belongs to the runt domain family of transcription factors that act as master regulators of gene expression in major developmental pathways. In mammals the family includes three genes, RUNX1, RUNX2 and RUNX3. Here, we describe a comparative analysis of the human chromosome 1p36.1 encoded RUNX3 and mouse chromosome 4 encoded Runx3 genomic regions. The analysis revealed high similarities between the two genes in the overall size and organization and showed that RUNX3/Runx3 is the smallest in the family, but nevertheless exhibits all the structural elements characterizing the RUNX family. Detailed sequence analysis placed the two genes at a GC-rich H3 isochore with a sharp transition of GC content between the gene sequence and the downstream intergenic region. Two large conserved CpG islands were found within both genes, one around exon 2 and the other at the beginning of exon 6. Recently, lack of RUNX3 function was found to be associated with genesis and progression of gastric carcinoma. transcriptional inactivation of RUNX3 by promoter hypermethylation may participate in the stomach carcinogenesis。Data have demonstrated its function to be thoroughly involved the neurogenesis of the dorsal root ganglia, T-cell differentiation and tumorigenesis of gastric epithelium. As a TGF-beta target, RUNX3 protein is believed to be involved in TGF-beta-mediated tumorsuppressor pathway; however, little is known about its role in apoptosis. According to recent data reported by Yamamura et al., RUNX3 interacts with FoxO3a/FKHRL1 expressed in gastric cancer cells to activate Bim and induce apoptosis. The cooperation between RUNX3 and the PI3K/Akt signaling pathway component FoxO3a/FKHRL1 suggests the putative role of RUNX3 in the homoeostasis of gastric cells and in stomach cancer control. Here we discuss recent breakthroughs in our understanding of the mechanisms of RUNX3 in gastric malignancy and comment on possible future trends and perspectives.We are To investigate methylation status of Runx3 in gastric carcinomaand corresponding non-neoplastic gastric, to explore the methylation status of Runx3 is importance in the development of gastric carcinoma. the Methods is that The methylation status of Runx3 gene was examined by methylation-specific polymerase chain reaction (MS-PCR). The Resul is that Methylation of Runx3 promoter region was confirmed in 87% (26/30) specimens of gastric carcinoma and 47% (14/30) in corresponding non-neoplastic gastric we Conclusion that High frequent hypermthylation were found in the gastric carcinoma, Methylation of runx3 in the corresponding non-neoplastic gastric is less than the gastric carcinoma (p<0.05), The methylation status of Runx3 gene is important role in the development and infiltration of Gastric cancer.it is a hope for the clinical stages and a target of gene therapy.RUNX3 is a Runt domain transcription factor that interacts with Smad proteins, suggesting that it may play an important role in TGF signalling. This gene is a region commonly deleted in a wide variety of human cancers, including lung cancer and breast cancer DNA methylation in the 5' region is emerging as the primary mechanism of TSG inactivation Aberrant methylation of the HPP1 and RUNX3genehas been demonstrated in.gastrointestinal and other human tumours...
Keywords/Search Tags:Non-neoplastic
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