Epigenetic modification of DKK-1 affects the Wnt pathway activity in pancreatic cancers
AIM:To investigate Wnt pathway activity in pancreatic cancer cell lines.To observe the methylation of Wnt antagonist(DKK-1)and its possible function on pancreatic cancer.METHODS:Wnt pathway activity was detected through luciferase activit).The expression of Wnt antagonist(DKK-1)was detected with Reahime-PCR technique.MSP analysis was applied to observe the methylation of DICK-1.Gene recombination technique was applied to modulate the DKK-1 expression on pancreatic cancers.RESULTS:Abnormal Wnt activity was detected in pancreatic cancer cell lines.Compared with normal pancreas cell lines,Wnt activity and its target gene expression were upregulated.As the Wnt antagonist,DKK-1 mRNA level was obviously downregulated.MSP analysis confirmed that methylation of DKK-1 was detected in pancreatic cancer ceils.Methylated DKK-1 was found in several pancreatic cancer cells.With 5-aza-2'-deoxycytidine treatment,the expression of DKK-1 could be repaired.With the upregulation of DKK-1 expression,the Wnt pathway activity was inhibited.On the contrary,with the knockdown of DKK-1 expression,the Wnt pathway activity was increased.CONCLUSION:The Wnt pathway was deregulated in pancreatic cancer cells.Epigenetic Modification of DKK-1,the Wnt antagonist,was considered to contribute to active Wnt pathway in pancreatic cancers.
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NSTL
万方数据
维普
