胰腺癌中 ATP 结合盒基因的表达和启动子甲基化分析。

Expression and promoter methylation analysis of ATP-binding cassette genes in pancreatic cancer.

机构信息

Laboratory of General Surgery, Department of Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, PR China.

出版信息

Oncol Rep. 2012 Jan;27(1):265-9. doi: 10.3892/or.2011.1475. Epub 2011 Sep 28.

DOI:10.3892/or.2011.1475

PMID:21956451

Abstract

We investigated the relationship of ABCB1/MDR1, ABCC1/MRP1 and ABCG2/BCRP expression and promoter methylation with pancreatic cancer tumorigenesis and drug resistance. Gemcitabine-resistant pancreatic cancer cells, SW1990/GZ (33.3-fold increased resistance), were obtained by treating SW1990 cells with gemcitabine. The expression of ABCB1/MDR1, ABCC1/MRP1 and ABCG2/BCRP was determined by quantitative real-time RT-PCR in the cell lines, 3 normal pancreatic tissues, 15 human pancreatic cancer samples and 15 adjacent tissues. Promoter methylation was determined in cell lines by bisulfite genomic sequencing. ABCB1/MDR1, ABCC1/MRP1 and ABCG2/BCRP were upregulated in SW1990 and SW1990/GZ compared with normal pancreatic tissue, and expression in SW1990/GZ was significantly higher than in SW1990 cells. ABCB1/MDR1, ABCC1/MRP1 and ABCG2/BCRP were upregulated in pancreatic 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 pancreatic cancer tumorigenesis and drug resistance in a mechanism that is independent of promoter methylation.

摘要

我们研究了 ABCB1/MDR1、ABCC1/MRP1 和 ABCG2/BCRP 的表达和启动子甲基化与胰腺癌发生和耐药的关系。通过用吉西他滨处理 SW1990 细胞，获得了对吉西他滨耐药的胰腺癌细胞系 SW1990/GZ（耐药性增加了 33.3 倍）。通过定量实时 RT-PCR 在细胞系、3 个正常胰腺组织、15 个人胰腺癌样本和 15 个相邻组织中测定了 ABCB1/MDR1、ABCC1/MRP1 和 ABCG2/BCRP 的表达。通过亚硫酸氢盐基因组测序在细胞系中测定了启动子甲基化。与正常胰腺组织相比，ABCB1/MDR1、ABCC1/MRP1 和 ABCG2/BCRP 在 SW1990 和 SW1990/GZ 中上调，并且 SW1990/GZ 中的表达明显高于 SW1990 细胞。与相邻组织相比，ABCB1/MDR1、ABCC1/MRP1 和 ABCG2/BCRP 在胰腺癌组织中上调。ABCB1/MDR1、ABCC1/MRP1 和 ABCG2/BCRP 的启动子在所有细胞系中均呈低甲基化状态。ABCB1/MDR1、ABCC1/MRP1 和 ABCG2/BCRP 的表达与胰腺癌的发生和耐药相关，这种相关性与启动子甲基化无关。