ppENKGene Methylation Status in the Development of Pancreatic Carcinoma

Abstract

Objective. To explore the association of hypermethylation of the proenkephalin gene (ppENK) with pancreatic carcinoma and to identify the effects of a demethylating agent on pancreatic cell lines.Method. Human pancreatic cancer tissues and five pancreatic carcinoma cell lines, as well as normal pancreatic tissue, were used.ppENKmethylation status was detected by MS-PCR (methylation-specific PCR).Results. Methylation ofppENKwas detected in 90.3% (28/31) of the human pancreatic carcinoma tissues but was not seen in normal pancreatic tissue. There was no correlation between the extent of methylation ofppENKand the clinicopathological features of the pancreatic carcinomas. MethylatedppENKwas detected in all the pancreatic cancer cell lines and was associated with loss of mRNA expression in the pancreatic carcinoma cell lines and normal pancreatic tissue. After treatment with 5-aza-dC, methylatedppENKwas not detected and the inhibition ofppENKmRNA expression was reversed.Conclusions. Inhibition ofppENKexpression by a change in its methylation status plays an important role in pancreatic carcinogenesis.ppENKmethylation is thus an important molecular event that distinguishes pancreatic carcinoma tissue from normal pancreatic tissue. Effects on cell growth, apoptosis, and the cell cycle may contribute to changes ofppENKmethylation status.