Aberrant methylation of Ras association domain family 1A promoter CpG island in pancreatic cancer cell line BxPC3 and tissues / 中华胰腺病杂志

ABSTRACT

Objective To determine the methylation status and expression of Ras association domain family 1A (RASSF1A), and the possible effect between promoter aberrant methylation and pathogenesis of pancreatic cancer. Methods The methylation status of RASSF1A promoter CpG island (CGI) pancreatic cancer cell line BxPC3 was detected in 5 cases of normal pancreatic tissue and 13 pairs of pancreatic cancer tissues (tumor and peri-tumor) by using COBRA (combined bisulfite restriction analysis) and the methylation rate was calculated. The RASSF1A mRNA expression of BxPC3 was compared between pre- and post-treatment of the inhibitor of DNA methyltransferase (5-Aza-2-deoxycitydine, 5-Aza-dC). Results The average methylation rate of RASSF1A promoter CGI was 62.90% in BXPC3, 9.14% in normal pancreas, 53.79% in peri-tumors (TP), and 55.82% in tumors. The methylation rates in port-tumors and tumors were significantly increased when compared with that of normal pancreas (P < 0.01), while there was no significant difference between in peri-tumors and tumors (P > 0.05). After 5-Aza-dC treatting BxPC3 cells, the methylation rates decreased to 42.5% (P < 0. 05) and RASSF1A mRNA expression was enhanced. Conclusions Aberrant hypermethylation of RASSF1A promoter CGI could be considered as an early event in the process of pancreatic cancer and participates in the pathogenesis of pancreatic cancer.