Frequent promoter methylation and gene silencing of CDH13 in pancreatic cancer.

It has recently been reported that CDH13 expression is silenced by aberrant methylation of the promoter region in several cancers. We examined the methylation status of the CDH13 gene in pancreatic cancer using methylation-specific PCR (MSP), and detected aberrant methylation of CDH13 in all 6 pancreatic cancer cell lines examined. To confirm the status of the CDH13 gene in relation to the methylation pattern, we next examined CDH13 expression in these cell lines using reverse transcription (RT)-PCR. As expected, no CDH13 expression was detected in any of the 6 pancreatic cancer cell lines. Moreover, 5-aza-2'-deoxycytidine (5-aza-dC) treatment of CDH13-methylated cell lines led to restoration of CDH13 expression. Among primary pancreatic cancers, 19 of 33 (58%) cases exhibited CDH13 methylation, while no cases exhibited it in corresponding normal pancreatic tissues. CDH13 methylation was detected even in relatively early pancreatic cancers, such as stage II cancers and cancers less than 2 cm in diameter. Our results suggest that the aberrant methylation of CDH13 occurs frequently in pancreatic cancer, even at a relatively early stage.