Promoter methylation regulates tazarotene-induced gene-1 expression in human pancreatic cancer

Objective To investigate the expression of tazarotene-induced gene-1 (TIG1) in pancreatic cancer and the methylation status of TIG1 promoter in pancreatic cancer cells. Methods Total 67 cases of pancreatic carcinoma and 67 cases of paired adjacent tissue were collected as the object of study. TIG1 protein was detected by immunohistochemical SP method to analyze the difference of expression of TIG1 in cancer tissues and paired adjacent tissue. Methylation status of TIG1 promoter in pancreatic cancer cell lines PANC1, BxPC3 and SW1990 were examined by Bisulfite sequencing PCR (BSP). The levels of TIG1 mRNA in these cells were identified by RT-PCR. PANC1 BxPC3 and SW1990 cells were treated with the demethylation agent, 5-aza-dC, at different concentrations, and the changes of TIG1 mRNA in these cells were examined by RT-PCR. Results The expression of TIG1 in cancer tissues was lower than that in paired adjacent tissue (P<0.05), and the expression of TIG1 was not correlated with size stage and lymph node metastasis of pancreatic cancer, but there was correlation with location (P<0.05). (92±2)% and (86±2)% of TIG1 CpG sites were methylated in BxPC3 and SW1990 cells respectively. While the ratio was (40±2)% in PANC1 cells. Decreased TIG1 mRNA can be restored in BxPC3 and SW1990 after treatment with 5-aza-dC, while there was no significant change in PANC1 cells. Conclusion The expression of TIG1 in cancer tissues is lower than that in paired adjacent tissue. There is difference in the expression of TIG1 in different parts of pancreatic carcinoma. Decreased TIG1 in BxPC3 and SW1990 is significantly correlated with promoter hypermethylation, suggesting that promoter hypermethylation may play an important role in the regulation of TIG1.