Androgen induces expression of the multidrug resistance protein gene MRP4 in prostate cancer cells.
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.
Cai
C
C
Department of Biological Sciences, University of Toledo, Toledo, OH 43606, USA.
Omwancha
J
J
Hsieh
C-L
CL
Shemshedini
L
L
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D013196:Dihydrotestosterone / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000494:pharmacology; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics* / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D011944:Receptors, Androgen / Q000502:physiology; D014407:Tumor Cells, Cultured
D000964:Antimetabolites, Antineoplastic; D013196:Dihydrotestosterone; D008727:Methotrexate; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D011944:Receptors, Androgen; C073492:ABCC4 protein, human