Disease relevance of ABCB1

• CONCLUSIONS: Our results suggest that the effects of CSA may be divided into two groups: ABCB1-independent (direct injury), and ABCB1-dependent toxicity, due to modulation of its activity [1].
• De novo MDR1 transcript expression was independent of response to therapy in dogs with lymphoma [2].
• Here, we show that leukemias associated with retroviral expression of MDR1 depend on high vector dose, and involve the selection of clones with combinatorial insertional mutagenesis of proto-oncogenes or other signaling genes [3].
• Human HeLa or canine CTAC cells, transduced with GALV env pseudotyped LgMIN at an MOI of less than 0.01 to ensure 1 proviral copy/genome, were selected with either G418 for neo expression or colchicine for MDR1 expression [4].
• Comparably high MDR-1 RNA levels were measured in all normal liver tissues, one of the lymphomas and a cholangiocarcinoma [5].

High impact information on ABCB1

• A mutation in the canine multidrug resistance gene, MDR1, has previously been associated with drug sensitivities in two breeds from the collie lineage [6].
• In contrast, no such complications or MDR1-associated alterations of hematopoiesis were observed in numerous other studies exploring MDR1 gene transfer into cell lines, mice, dogs, nonhuman primates, and human subjects [3].
• BSEP, MDR1, and MDR2 ATP binding cassette transporters are targeted to the apical (canalicular) membrane of hepatocytes, where they mediate ATP-dependent secretion of bile acids, drugs, and phospholipids, respectively [7].
• A yeast two-hybrid screen of a rat liver cDNA library identified the myosin II regulatory light chain, MLC2, as a binding partner for BSEP, MDR1, and MDR2 [7].
• These results indicated suppression of expression of vector-derived MDR1 in HeLa cells, in contrast with CTAC cells [4].

Chemical compound and disease context of ABCB1

• Expression of MDR1 mRNA correlates with in vitro drug sensitivity but does not correlate with in vivo doxorubicin sensitivity in canine lymphoma [2].
• Loperamide toxicity in a collie with the MDR1 mutation associated with ivermectin sensitivity [8].

Biological context of ABCB1

• To explore the basis of this phenotype, we analyzed the canine P-glycoprotein-encoding MDR1 gene, and we report the first characterization of the cDNA for wild-type (Beagle) P-glycoprotein [9].
• RESULTS: Canine transcript was 4.5 Kb with 93% sequence homology to human MDR1, and 90% homology to mouse and hamster equivalent genes [2].
• BACKGROUND: Overexpression of the MDR1 gene often contributes to antineoplastic drug resistance [2].
• Poor expression of MDR1 transgene in HeLa cells by bicistronic Moloney murine leukemia virus-based vector [4].
• It is assumed that PKC and ras oncogene regulate mdr1 gene expression through at least partially distinct signalling pathways [10].

Anatomical context of ABCB1

• Studies using transfected MDCK cell lines revealed an active efflux component attributable to MDR1 (ABCB1) [11].
• MDR1 (ABCB1) P-glycoprotein exerts a protective function in the blood-brain barrier thereby limiting the entry of many drugs and other xenobiotics to the central nervous system [12].
• Notably, LLC-PK1 cells displayed little activity attributable to either MDR1 and MRP1, thus making them suitable for the expression of these efflux pumps [13].
• In this study, we evaluated the permeability of a series of phosphoramidate triester prodrugs of the anti-HIV drug 2',3'-didehydro-2',3'-dideoxythymidine across monolayers of Caco-2, Madin-Darby canine kidney (MDCKII) epithelial cell line, and its recombinant clone containing the human MDR1/P-gp gene (MDR1-MDCKII) [14].
• Are MDCK cells transfected with the human MDR1 gene a good model of the human intestinal mucosa [15]?

Associations of ABCB1 with chemical compounds

• Differential interaction of 3-hydroxy-3-methylglutaryl-coa reductase inhibitors with ABCB1, ABCC2, and OATP1B1 [16].
• To determine the effect of cholesterol depletion on P-gp, Madin Darby canine kidney (MDCK) cells, transfected with the mdr1 gene (MDR1-MDCK cells), were treated with methyl-beta-cyclodextrin (MbetaCD) [17].
• The system was connected to dogs intoxicated with digoxin, a representative substrate of MDR-1 [18].
• Inhibition of the MDR1 transporter by new phenothiazine derivatives [19].
• Rhodamine 123 appeared to "stimulate" the polarized efflux of Hoechst 33342 across MDCK-MDR1 cell monolayers [20].

Analytical, diagnostic and therapeutic context of ABCB1

• MATERIALS AND METHODS: The abundance of the canine MDR1 transcript was assessed in three resistant cell lines and in pretreatment canine lymphoma using semi-quantitative RT/PCR [2].
• BACKGROUND: We have recently developed a unique hybrid artificial kidney, where the proximal tubular cell line, over-expressing multidrug resistance protein, MDR-1 (PCTL-MDR), was cultured on hollow fibers [18].
• The effectiveness of the compounds on the MDR1 mediated calcein-AM efflux, ATPase activity, and colchicine resistance was proven by microplate assays and flow cytometry using recombinant and control cell lines [19].
• Polymerase chain reaction (PCR) primers were designed to amplify a 1,061-base pair region of the MDR1 gene [21].
• Development of a PCR-based diagnostic test detecting a nt230(del4) MDR1 mutation in dogs: verification in a moxidectin-sensitive Australian Shepherd [22].

References