Aberrant DNA methylation of the 5′ upstream region of Tslc1 gene in hamster pancreatic tumors

To determine if the Tslc1 gene is involved in pancreatic carcinogenesis, the expression level of Tslc1 and the DNA methylation status of its 5′ upstream region were investigated in pancreatic duct adenocarcinomas (PDAs) induced in hamsters by N-nitrosobis(2-oxopropyl)amine (BOP). Female Syrian golden hamsters received 70 mg/kg of BOP followed by repeated exposure to an augmentation pressure regimen consisting of a choline-deficient diet combined with ethionine-methionione-BOP injection. Total RNA was extracted from 11 PDAs and the level of Tslc1 expression was measured in each by real-time quantitative reverse transcription (RT)-polymerase chain reaction (PCR). The expression level of Tslc1 was significantly reduced in PDAs (p < 0.05) compared with normal pancreatic tissues. In order to assess the DNA methylation status of the 5′ upstream region of Tslc1, bisulfite sequencing was performed. Although this region was unmethylated in normal pancreatic tissue, it was highly methylated in four PDAs, correlating with reduced Tslc1 expression. These results suggest that a reduction in the expression of Tslc1 due to aberrant DNA methylation might be involved in the development of PDAs induced in hamsters by BOP.