Epigenetic inactivation of @entity460 -sensing receptor in XXXX .

@entity1 @entity1631 @entity5 @entity3546 @entity3996 @entity460 @entity14 @entity141 @entity652 @entity694 @entity1487 @entity11508
@entity141 is a chemopreventive agent for @entity694 . Ion transport systems are often altered in @entity1 @entity5 . The aim of this study was to clarify the alterations of @entity460 -sensing receptor ( @entity1631 ), a member of the G protein-coupled receptor family, in @entity14 . We analyzed the expression of @entity1631 in @entity14 cell lines and in @entity5 and @entity652 tissues by RT-PCR and immunostaining. In addition, we analyzed methylation of the @entity1631 promoter by using bisulfite sequence analysis and methylation-specific PCR. @entity1631 mRNA and protein expression was significantly downregulated in most of the @entity5 cell lines. CpG islands were densely methylated in @entity5 cell lines with reduced @entity1631 mRNA expression. Treatment with a demethylating agent, @entity11508 , and/or a histone deacetylase inhibitor, @entity3996 , restored @entity1631 expression in the @entity5 cell lines. Disruption of @entity1631 expression in @entity1631 -unmethylated HCT-8 cells blocked the enhancing effect of @entity141 on the cytotoxic response to @entity1487 . @entity1631 expression was observed in normal colonic epithelial cells and was retained in most @entity652 tissues. @entity1631 mRNA and protein expression was significantly downregulated in @entity5 tissues. There was an inverse relationship between @entity1631 expression and degree of differentiation. Immunohistochemical @entity1631 staining was reduced more predominantly in less-differentiated @entity5 tissues and/or in @entity5 cells at the invasive front, where nuclear/cytoplasmic @entity3546 was often localized. @entity1631 methylation was detected in 69% of @entity14 tissues and 90% of lymph node metastatic tissues and was significantly correlated with reduced @entity1631 expression. @entity1631 methylation was also detected in 32% of advanced @entity652 tissues but was detected in only 9% of @entity652 tissues and was not detected in hyperplastic polyp tissues. @entity1631 methylation seems to occur at an early stage and progress in @entity14 . The results suggest that epigenetic inactivation of @entity1631 has an important role in @entity14 .
