Abstract

We investigated the relationship ofABCB1/MDR1, ABCC1/MRP1 and ABCG2/BCRP expression and promoter methylation withpancreatic cancer tumorigenesis and drug resistance. Gemcitabine-resistantpancreatic cancer cells, SW1990/GZ (33.3-fold increased resistance), wereobtained by treating SW1990 cells with gemcitabine. The expression ofABCB1/MDR1, ABCC1/MRP1 and ABCG2/BCRP was determined by quantitative real-timeRT-PCR in the cell lines, 3 normal pancreatic tissues, 15 human pancreaticcancer samples and 15 adjacent tissues. Promoter methylation was determined incell lines by bisulfite genomic sequencing. ABCB1/MDR1, ABCC1/MRP1 andABCG2/BCRP were upregulated in SW1990 and SW1990/GZ compared with normalpancreatic tissue, and expression in SW1990/GZ was significantly higher than inSW1990 cells. ABCB1/MDR1, ABCC1/MRP1 and ABCG2/BCRP were upregulated inpancreatic cancer tissues, compared to adjacent tissues. The ABCB1/MDR1,ABCC1/MRP1 and ABCG2/BCRP promoter were hypomethylated in all the cell lines.ABCB1/MDR1, ABCC1/MRP1 and ABCG2/BCRP expression correlated with pancreaticcancer tumorigenesis and drug resistance in a mechanism that is independent ofpromoter methylation.