Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P33527 (ABCC1)
 1,164 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Drug-resistant sublines of the human U-937 myeloid leukemia cell line were selected in doxorubicin concentrations of 10, 40, and 200 ng/mL (designated U-A10, U-A40, and U-A200, respectively). Northern blot analysis showed overexpression of the multidrug resistance-associated protein (MRP) gene, but not MDR1, in U-A10 cells as compared with parental U-937 cells. Prolonged passage of U-A10 cells in 10 ng/mL of doxorubicin had little effect on MRP RNA levels, but increased MDR1 expression. The U-A40 and U-A200 cells, derived by selection of U-A10 cells, showed high levels of both MRP and MDR1 expression. None of the drug-resistant cell lines showed MRP or MDR1 gene amplification as judged by Southern blot analysis. U-A10 cells exhibited minimal decreased net accumulation of anthracycline, whereas U-A40 and U-A200 cells showed more significantly decreased drug accumulation as compared with U-937 cells. Subcellular anthracycline accumulation in U-937 cells as determined by fluorescence microscopy showed daunorubicin fluorescence predominately in the nucleus. However, the drug-resistant cell lines showed minimal nuclear drug accumulation with marked redistribution of drug into a vesicular compartment. Treatment with sodium azide/2-deoxyglucose, 2,4-dinitrophenol, or monensin, but not verapamil, abolished the vesicular accumulation. These studies in doxorubicin-selected U-937 cells indicate that induction of MRP overexpression occurs before that for the MDR1 gene. In addition, the drug-resistant cells possess an energy-dependent redistribution of anthracyclines into a nonnuclear vesicular compartment.
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PMID:Expression of the multidrug resistance associated protein and P-glycoprotein in doxorubicin-selected human myeloid leukemia cells. 794 84

In this study, we have examined the in vitro chemosensitizing activity of difloxacin, a quinolone antimicrobial agent, in the multidrug-resistant human myeloid leukemia HL-60/AR cell line. HL-60/AR cells were found to overexpress multidrug resistance-associated protein (MRP) mRNA as compared to HL-60 cells. Difloxacin, in a concentration-dependent manner, increased the sensitivity of HL-60/AR cells to daunorubicin, adriamycin, and vincristine, and partially corrected the altered drug transport. In addition, difloxacin corrected subcellular distribution of adriamycin by inducing redistribution of the drug from the perinuclear region to the nucleus in HL-60/AR cells. The chemosensitizing effect of difloxacin was observed at clinically achievable concentrations. We conclude that difloxacin is an effective chemosensitizer of MRP-associated multidrug-resistant tumor cells and is a potential candidate for clinical use to reverse multidrug resistance.
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PMID:Difloxacin reverses multidrug resistance in HL-60/AR cells that overexpress the multidrug resistance-related protein (MRP) gene. 853 27

Development of multidrug resistance (MDR) in cancer cells is associated with an overexpression of ATP-binding cassette proteins [e.g. P-glycoprotein (P-gp), multidrug resistance-associated protein (MRP)] and with decreased chemotherapeutic agent-induced apoptosis. In this study, we investigated whether MDR in cancer cells was associated with altered expression of genes regulating apoptosis using a drug sensitive human myeloid leukemia cell line (HL60), and its MDR sublines, overexpressing MRP (HL60/AR) or P-gp (HL60/taxol). Expression of apoptotic Genes was examined at the protein level by flow cytometry and at the mRNA level by reverse transcriptase-polymerase chain reaction (RT-PCR). We observed that the MDR cells either did not express or expressed a reduced level of the apoptosis promoters Fas, Bcl-x(s), and Bax, whereas expression of the apoptosis repressor Bcl-x, was increased. Both vincristine and anti-Fas monoclonal antibody induced apoptosis in HL60 cells but failed to do so in both MDR cell lines. These data suggest that acquired MDR in cancer cells, regardless of the type of overexpressed ABC transporter, may be associated with increased expression of antipeptidic genes and decreased expression of pro-apoptotic Genes.
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PMID:Altered expression of the genes regulating apoptosis in multidrug resistant human myeloid leukemia cell lines overexpressing MDR1 or MRP gene. 2152 88

Despite the success of imatinib mesylate (IM) in the treatment of chronic myeloid leukemia (CML), approximately 30% of patients are resistant to therapy, mostly due to unknown causes. To profile the expression signatures of drug transporters throughout IM therapy and correlate them with resistance, we quantified mRNA expression levels of the SLC22A12, ABCB1, ABCC1, ABCG2 and MVP genes in consecutive samples from peripheral blood or bone marrow of CML patients who were either responsive or resistant to IM. Additionally we identified and quantified BCR-ABL1 transcript variants and analyzed 1236T>C ABCB1 and 480G>C SLC22A1 polymorphisms. A relationship between the type of BCR-ABL1 transcript or ABCB1 or SLC22A1 genotype and response to treatment was not discovered. However, the studied genes had higher expression levels in follow-up compared to the diagnostic samples, demonstrating a possible induction in expression. IM-sensitive patients presented significantly higher values of SLC22A1 expression, suggesting higher drug influx. Most importantly, while responding patients demonstrated stable expression signatures in consecutive samples, there was considerable variation in IM-resistant patients, indicating that single point sampling expression signatures are not reliable in predicting clinical outcomes or prognostic features in these patients. Studies that assessed consecutive samples from CML patients in order to evaluate the variation in expression levels of transporter genes are limited yet our study emphasizes the importance of such approaches.
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PMID:Instability of mRNA expression signatures of drug transporters in chronic myeloid leukemia patients resistant to imatinib. 2322 16