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

被引:41
作者
Cai, C. [1 ]
Omwancha, J. [1 ]
Hsieh, C-L [1 ]
Shemshedini, L. [1 ]
机构
[1] Univ Toledo, Dept Biol Sci, Toledo, OH 43606 USA
基金
美国国家卫生研究院;
关键词
androgen receptor; androgen; multidrug resistance; MRP4;
D O I
10.1038/sj.pcan.4500912
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:39 / 45
页数:7
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