雄激素诱导前列腺癌细胞中多药耐药蛋白基因MRP4的表达。

Androgen induces expression of the multidrug resistance protein gene MRP4 in prostate cancer cells.

作者信息

Cai C, Omwancha J, Hsieh C-L, Shemshedini L

机构信息

Department of Biological Sciences, University of Toledo, Toledo, OH 43606, USA.

出版信息

Prostate Cancer Prostatic Dis. 2007;10(1):39-45. doi: 10.1038/sj.pcan.4500912. Epub 2006 Sep 26.

DOI:10.1038/sj.pcan.4500912

PMID:17003774

Abstract

Multidrug resistance-associated proteins (MRPs) may mediate multidrug resistance in tumor cells. Using a gene array analysis, we have identified MRP4 as an androgen receptor (AR)-regulated gene. Dihydrotestosterone induced MRP4 expression in both androgen-dependent and -independent LNCaP cells, whereas there was little detectable expression in PC-3 or normal prostate epithelial cells. Disruption of MRP4 expression renders LNCaP cells more sensitive to the cytotoxic effects of methotrexate but not etoposide. Analysis of human tissues showed detectable MRP4 expression only in metastatic prostate cancer. These results suggest that AR induction of MRP4 mediates resistance of PC cells to nucleotide-based chemotherapeutic drugs.

摘要

多药耐药相关蛋白（MRPs）可能介导肿瘤细胞的多药耐药性。通过基因阵列分析，我们已确定MRP4是一种雄激素受体（AR）调控的基因。双氢睾酮在雄激素依赖和非依赖的LNCaP细胞中均诱导MRP4表达，而在PC-3或正常前列腺上皮细胞中几乎检测不到表达。MRP4表达的破坏使LNCaP细胞对甲氨蝶呤的细胞毒性作用更敏感，但对依托泊苷不敏感。对人体组织的分析表明，仅在转移性前列腺癌中可检测到MRP4表达。这些结果表明，AR诱导的MRP4介导了前列腺癌细胞对核苷类化疗药物的耐药性。