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

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.

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Acknowledgements

We thank Dr M-F Lin for providing the C33 and C81 cells and Dr K Johnson for anti-E-cadherin antibodies. This work was supported by grants from the National Institutes of Health and Ohio Cancer Research Associates.

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Correspondence to L Shemshedini.

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Cai, C., Omwancha, J., Hsieh, CL. et al. Androgen induces expression of the multidrug resistance protein gene MRP4 in prostate cancer cells. Prostate Cancer Prostatic Dis 10, 39–45 (2007). https://doi.org/10.1038/sj.pcan.4500912

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