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. ppENK methylation status was detected by MS-PCR (methylation-specific PCR). Results. Methylation of ppENK was 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 of ppENK and the clinicopathological features of the pancreatic carcinomas. Methylated ppENK was 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, methylated ppENK was not detected and the inhibition of ppENK mRNA expression was reversed. Conclusions. Inhibition of ppENK expression by a change in its methylation status plays an important role in pancreatic carcinogenesis. ppENK methylation 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 of ppENK methylation status.
Highlights
Pancreatic carcinoma is highly malignant and has a poor prognosis
We examined expression of ppENK using RT-poly-merase chain reaction (PCR) in the 5 pancreatic cell lines. ppENK mRNA was detected in normal pancreatic tissue but not in the five pancreatic carcinoma cell lines (Panc-1, Pupan-1, Aspc-1, PC3, and SW1990) (Figure 2)
The ppENK gene encodes met-enkephalin, which is a tonically active inhibitory factor that interacts with the opioid growth factor receptor
Summary
The overall 5-year survival rate for pancreatic cancer does not exceed 5% in most studies, because it is generally diagnosed too late to allow surgery, which is still considered a curative treatment for pancreatic cancer. The incidence of pancreatic cancer has steadily increased in recent years. Its pathogenesis is not understood, and novel treatments are urgently needed [1]. The human ppENK gene has been localized to chromosome 8, at q23-q24, and consists of four transcribed exons and three introns. It is a neuropeptide transmitter gene and encodes Met-enkephalin, which is a topically active inhibitor of pancreatic cancers that interacts with the opioid growth factor receptor [2, 3]
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