Structural, mechanistic and clinical aspects of MRP1.

The cDNA encoding ATP-binding cassette (ABC) multidrug resistance protein MRP1 was originally cloned from a drug-selected lung cancer cell line resistant to multiple natural product chemotherapeutic agents. MRP1 is the founder of a branch of the ABC superfamily whose members (from species as diverse as plants and yeast to mammals) share several distinguishing structural features that may contribute to functional and mechanistic similarities among this subgroup of transport proteins. In addition to its role in resistance to natural product drugs, MRP1 (and related proteins) functions as a primary active transporter of structurally diverse organic anions, many of which are formed by the biotransformation of various endo- and xenobiotics by Phase II conjugating enzymes, such as the glutathione S-transferases. MRP1 is involved in a number of glutathione-related cellular processes. Glutathione also appears to play a key role in MRP1-mediated drug resistance. This article reviews the discovery of MRP1 and its relationships with other ABC superfamily members, and summarizes current knowledge of the structure, transport functions and relevance of this protein to in vitro and clinical multidrug resistance.

[1]  I. Pastan,et al.  Mechanism of Action of Human P-glycoprotein ATPase Activity , 1998, The Journal of Biological Chemistry.

[2]  P. Gros,et al.  Epitope insertion favors a six transmembrane domain model for the carboxy-terminal portion of the multidrug resistance-associated protein. , 1998, Biochemistry.

[3]  S. Cole,et al.  Multidrug resistance mediated by the multidrug resistance protein (MRP) gene. , 1996, Biochemical pharmacology.

[4]  D. Roden,et al.  Human MRP3 transporter: identification of the 5'-flanking region, genomic organization and alternative splice variants. , 1999, Biochimica et biophysica acta.

[5]  A. Duncan,et al.  Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line. , 1992, Science.

[6]  R. Evers,et al.  The human multidrug resistance protein MRP1 translocates sphingolipid analogs across the plasma membrane. , 1999, Journal of cell science.

[7]  T. Massey,et al.  ATP-dependent transport of aflatoxin B1 and its glutathione conjugates by the product of the multidrug resistance protein (MRP) gene. , 1997, Molecular pharmacology.

[8]  R. Shoemaker,et al.  Overlapping phenotypes of multidrug resistance among panels of human cancer‐cell lines , 1996, International journal of cancer.

[9]  D. Bell,et al.  Isolation of MOAT-B, a widely expressed multidrug resistance-associated protein/canalicular multispecific organic anion transporter-related transporter. , 1998, Cancer research.

[10]  C. Higgins,et al.  ABC transporters: from microorganisms to man. , 1992, Annual review of cell biology.

[11]  G. Tusnády,et al.  Membrane topology distinguishes a subfamily of the ATP‐binding cassette (ABC) transporters , 1997, FEBS letters.

[12]  E. de Vries,et al.  Role of multidrug resistance protein (MRP) in glutathione S-conjugate transport in mammalian cells. , 1996, Journal of hepatology.

[13]  J. Lankelma,et al.  Modulation by (iso)flavonoids of the ATPase activity of the multidrug resistance protein , 1997, FEBS letters.

[14]  André Goffeau,et al.  Complete inventory of the yeast ABC proteins , 1997, Nature Genetics.

[15]  R L Juliano,et al.  A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants. , 1976, Biochimica et biophysica acta.

[16]  G. Giaccone,et al.  MRP gene overexpression in a human doxorubicin‐resistant SCLC cell line: Alterations in cellular pharmacokinetics and in pattern of cross‐resistance , 1995, International journal of cancer.

[17]  D. Keppler,et al.  ATP-dependent transport of bilirubin glucuronides by the multidrug resistance protein MRP1 and its hepatocyte canalicular isoform MRP2. , 1997, The Biochemical journal.

[18]  R. Evers,et al.  Transport of glutathione prostaglandin A conjugates by the multidrug resistance protein 1 , 1997, FEBS letters.

[19]  G. M. Wilson,et al.  Pharmacological characterization of multidrug resistant MRP-transfected human tumor cells. , 1994, Cancer research.

[20]  D. Hipfner,et al.  Detection of the M(r) 190,000 multidrug resistance protein, MRP, with monoclonal antibodies. , 1994, Cancer research.

[21]  A. Stringaro,et al.  Detection of P‐glycoprotein in the Golgi apparatus of drug‐untreated human melanoma cells , 1998, International journal of cancer.

[22]  C. Haest,et al.  Evidence for a role of the multidrug resistance protein (MRP) in the outward translocation of NBD-phospholipids in the erythrocyte membrane. , 1998, Biochimica et biophysica acta.

[23]  T. Ishikawa,et al.  Doxorubicin- and daunorubicin-glutathione conjugates, but not unconjugated drugs, competitively inhibit leukotriene C4 transport mediated by MRP/GS-X pump. , 1998, Biochemical and biophysical research communications.

[24]  S. Cole,et al.  Reconstitution of ATP-dependent Leukotriene C4 Transport by Co-expression of Both Half-molecules of Human Multidrug Resistance Protein in Insect Cells* , 1996, The Journal of Biological Chemistry.

[25]  J. Lecerf,et al.  Overexpression of the multidrug resistance-associated protein (MRP) gene in vincristine but not doxorubicin-selected multidrug-resistant murine erythroleukemia cells. , 1994, Cancer research.

[26]  D. Hipfner,et al.  Epitope mapping of monoclonal antibodies specific for the 190-kDa multidrug resistance protein (MRP). , 1998, British Journal of Cancer.

[27]  S. Aaronson,et al.  Expression complementary DNA library transfer establishes mrp as a multidrug resistance gene. , 1994, Cancer research.

[28]  R. Pieters,et al.  Relationship between major vault protein/lung resistance protein, multidrug resistance-associated protein, P-glycoprotein expression, and drug resistance in childhood leukemia. , 1998, Blood.

[29]  M. Ouellette,et al.  The amplified H circle of methotrexate‐resistant leishmania tarentolae contains a novel P‐glycoprotein gene. , 1990, The EMBO journal.

[30]  S. Cole.  The 1991 Merck Frosst Award. Multidrug resistance in small cell lung cancer. , 1992, Canadian journal of physiology and pharmacology.

[31]  P. Bosma,et al.  Congenital Jaundice in Rats with a Mutation in a Multidrug Resistance-Associated Protein Gene , 1996, Science.

[32]  S. Cole,et al.  Analysis of the intron-exon organization of the human multidrug-resistance protein gene (MRP) and alternative splicing of its mRNA. , 1997, Genomics.

[33]  R. Flavell,et al.  Double knockout of the MRP gene leads to increased drug sensitivity in vitro. , 1996, Cancer research.

[34]  T. Fujiwara,et al.  Cloning and chromosomal mapping of a novel ABC transporter gene (hABC7), a candidate for X-linked sideroblastic anemia with spinocerebellar ataxia , 1998, Journal of Human Genetics.

[35]  S. Cole,et al.  Multidrug Resistance Protein , 1998, The Journal of Biological Chemistry.

[36]  S. Cole,et al.  Function, evolution and structure of multidrug resistance protein (MRP). , 1997, Seminars in cancer biology.

[37]  S. Mirski,et al.  Multidrug resistance in a human small cell lung cancer cell line selected in adriamycin. , 1987, Cancer research.

[38]  A. Schroit,et al.  Transbilayer movement of NBD-labeled phospholipids in red blood cell membranes: outward-directed transport by the multidrug resistance protein 1 (MRP1). , 1998, Biochemistry.

[39]  P. Rabbitts,et al.  Amplification and expression of mdr1 gene in a multidrug resistant variant of small cell lung cancer cell line NCI-H69. , 1989, British Journal of Cancer.

[40]  A. Shapiro,et al.  Topological folding and proteolysis profile of P-glycoprotein in membranes of multidrug-resistant cells: implications for the drug-transport mechanism. , 1996, Biochemistry.

[41]  Y. Wang,et al.  Walker mutations reveal loose relationship between catalytic and channel-gating activities of purified CFTR (cystic fibrosis transmembrane conductance regulator). , 1999, Biochemistry.

[42]  H. Wheeler,et al.  Drug resistance mechanisms and MRP expression in response to epirubicin treatment in a human leukaemia cell line. , 1995, Leukemia research.

[43]  M. Yin,et al.  Carbamoylation of glutathione reductase by N,N-bis(2-chloroethyl)-N- nitrosourea associated with inhibition of multidrug resistance protein (MRP) function. , 1997, Biochemical pharmacology.

[44]  T. Ishikawa,et al.  ATP‐dependent leukotriene export from mastocytoma cells , 1991, FEBS letters.

[45]  Hiroshi Suzuki,et al.  Characterization of the Transport Properties of Cloned Rat Multidrug Resistance-associated Protein 3 (MRP3)* , 1999, The Journal of Biological Chemistry.

[46]  Y. Sugiyama,et al.  Excretion of GSSG and Glutathione Conjugates Mediated by MRP1 and CM0AT/MRP2 , 1998, Seminars in liver disease.

[47]  D. Keppler,et al.  Transport of glutathione, glucuronate, and sulfate conjugates by the MRP gene-encoded conjugate export pump. , 1996, Cancer research.

[48]  M. Kool,et al.  Expression of human MRP6, a homologue of the multidrug resistance protein gene MRP1, in tissues and cancer cells. , 1999, Cancer research.

[49]  R. Larson,et al.  Association of an inversion of chromosome 16 with abnormal marrow eosinophils in acute myelomonocytic leukemia. A unique cytogenetic-clinicopathological association. , 1983, The New England journal of medicine.

[50]  D. Keppler,et al.  ATP-dependent transport of glutathione S-conjugates by the multidrug resistance-associated protein. , 1994, Cancer research.

[51]  M. Akabas,et al.  Probing the Structural and Functional Domains of the CFTR Chloride Channel , 1997, Journal of bioenergetics and biomembranes.

[52]  G. F. Sullivan,et al.  The expression of drug resistance gene products during the progression of human prostate cancer. , 1998, Clinical cancer research : an official journal of the American Association for Cancer Research.

[53]  G. Tusnády,et al.  Membrane Topology and Glycosylation of the Human Multidrug Resistance-associated Protein (*) , 1996, The Journal of Biological Chemistry.

[54]  D. Kufe,et al.  Expression of the multidrug resistance associated protein and P-glycoprotein in doxorubicin-selected human myeloid leukemia cells. , 1994, Blood.

[55]  C. Willman,et al.  Deletion of gene for multidrug resistance in acute myeloid leukaemia with inversion in chromosome 16: prognostic implications , 1994, The Lancet.

[56]  P. Workman,et al.  Examination by laser scanning confocal fluorescence imaging microscopy of the subcellular localisation of anthracyclines in parent and multidrug resistant cell lines. , 1993, British Journal of Cancer.

[57]  B. Nielsen,et al.  Sequential coexpression of the multidrug resistance genes MRP and mdr1 and their products in VP-16 (etoposide)-selected H69 small cell lung cancer cells. , 1995, Cancer research.

[58]  K. Cowan,et al.  Multidrug resistance-associated protein gene overexpression and reduced drug sensitivity of topoisomerase II in a human breast carcinoma MCF7 cell line selected for etoposide resistance. , 1994, Cancer research.

[59]  D. Keppler,et al.  Transport of glutathione conjugates and glucuronides by the multidrug resistance proteins MRP1 and MRP2. , 1997, Biological chemistry.

[60]  T. Grogan,et al.  Multidrug resistance protein (MRP) expression in retinoblastoma correlates with the rare failure of chemotherapy despite cyclosporine for reversal of P-glycoprotein. , 1997, Cancer research.

[61]  G. Szakács,et al.  Functional Multidrug Resistance Protein (MRP1) Lacking the N-terminal Transmembrane Domain* , 1998, The Journal of Biological Chemistry.

[62]  S. Cole,et al.  Expression of the MRP and MDR1 multidrug resistance genes in small cell lung cancer. , 1997, Clinical cancer research : an official journal of the American Association for Cancer Research.

[63]  Y. Sugiyama,et al.  cDNA cloning and inducible expression of human multidrug resistance associated protein 3 (MRP3) 1 , 1998 .

[64]  K. Kohno,et al.  A human canalicular multispecific organic anion transporter (cMOAT) gene is overexpressed in cisplatin-resistant human cancer cell lines with decreased drug accumulation. , 1996, Cancer research.

[65]  J. Belli,et al.  Sequestration of doxorubicin in vesicles in a multidrug-resistant cell line (LZ-100). , 1994, Biochemical pharmacology.

[66]  R. Flavell,et al.  Evidence that the multidrug resistance protein (MRP) functions as a co-transporter of glutathione and natural product toxins. , 1997, Cancer research.

[67]  S. Cole,et al.  Multidrug resistance protein (MRP)-mediated transport of leukotriene C4 and chemotherapeutic agents in membrane vesicles. Demonstration of glutathione-dependent vincristine transport. , 1996, The Journal of biological chemistry.

[68]  R. Pirker,et al.  Immunocytochemical detection of the multidrug resistance-associated protein and P-glycoprotein in acute myeloid leukemia: impact of antibodies, sample source and disease status , 1997, Leukemia.

[69]  A. Faussat,et al.  Sequential emergence of MRP‐ and MDR1‐gene over‐expression as well as MDR1‐gene translocation in homoharringtonine‐selected K562 human leukemia cell lines , 1996, International journal of cancer.

[70]  S. Cohn,et al.  Expression of the gene for multidrug-resistance-associated protein and outcome in patients with neuroblastoma. , 1996, The New England journal of medicine.

[71]  D. Keppler,et al.  The MRP gene encodes an ATP-dependent export pump for leukotriene C4 and structurally related conjugates. , 1994, The Journal of biological chemistry.

[72]  H. Westerhoff,et al.  Anthracyclines modulate multidrug resistance protein (MRP) mediated organic anion transport. , 1997, Biochimica et biophysica acta.

[73]  G von Heijne,et al.  Determination of the distance between the oligosaccharyltransferase active site and the endoplasmic reticulum membrane. , 1993, The Journal of biological chemistry.

[74]  S. Cole,et al.  Structure and expression of the messenger RNA encoding the murine multidrug resistance protein, an ATP-binding cassette transporter. , 1996, Molecular pharmacology.

[75]  T. Ishikawa,et al.  ATP/Mg2+-dependent cardiac transport system for glutathione S-conjugates. A study using rat heart sarcolemma vesicles. , 1989, The Journal of biological chemistry.

[76]  D. Hipfner,et al.  Monoclonal Antibodies That Inhibit the Transport Function of the 190-kDa Multidrug Resistance Protein, MRP , 1999, The Journal of Biological Chemistry.

[77]  M. Barrand,et al.  Localisation of the multidrug resistance-associated protein, MRP, in resistant large-cell lung tumour cells. , 1995, Biochemical pharmacology.

[78]  T. Ishikawa,et al.  Coordinated Induction of MRP/GS-X Pump and γ-Glutamylcysteine Synthetase by Heavy Metals in Human Leukemia Cells* , 1996, The Journal of Biological Chemistry.

[79]  M. Flens,et al.  Characterization of a clonal human colon adenocarcinoma line intrinsically resistant to doxorubicin. , 1997, British Journal of Cancer.

[80]  D. Keppler,et al.  Drug resistance and ATP-dependent conjugate transport mediated by the apical multidrug resistance protein, MRP2, permanently expressed in human and canine cells. , 1999, Molecular pharmacology.

[81]  J. Trent,et al.  Pharmacological and biological evidence for differing mechanisms of doxorubicin resistance in two human tumor cell lines. , 1988, Cancer research.

[82]  S. Cole,et al.  ATP-dependent 17-Estradiol 17-(-D-Glucuronide) Transport by Multidrug Resistance Protein (MRP) , 1996, The Journal of Biological Chemistry.

[83]  G. Szakács,et al.  Nucleotide Occlusion in the Human Cystic Fibrosis Transmembrane Conductance Regulator , 1999, The Journal of Biological Chemistry.

[84]  T. Grogan,et al.  Standardization of a single-cell assay for sensitive detection of multidrug resistance protein expression in normal and malignant cells in archival clinical samples. , 1997, The Journal of laboratory and clinical medicine.

[85]  F. Baas,et al.  Altered MRP is associated with multidrug resistance and reduced drug accumulation in human SW-1573 cells. , 1995, British Journal of Cancer.

[86]  S. Natsugoe,et al.  The expression of multidrug resistance protein in human gastrointestinal tract carcinomas , 1998, Cancer.

[87]  R. Pirker,et al.  Multidrug resistance-associated protein in acute myeloid leukemia: No impact on treatment outcome. , 1997, Clinical cancer research : an official journal of the American Association for Cancer Research.

[88]  J. Zieleński,et al.  Cystic fibrosis: genotypic and phenotypic variations. , 1995, Annual review of genetics.

[89]  S. Cole,et al.  Multidrug resistance mediated by the ATP‐binding cassette transporter protein MRP , 1998, BioEssays : news and reviews in molecular, cellular and developmental biology.

[90]  G. Giaccone,et al.  Expression of drug resistance proteins in breast cancer, in relation to chemotherapy , 1997, International journal of cancer.

[91]  V. Ling,et al.  Functional intracellular P‐glycoprotein , 1998, International journal of cancer.

[92]  D. Keppler,et al.  ATP-dependent glutathione disulphide transport mediated by the MRP gene-encoded conjugate export pump. , 1996, The Biochemical journal.

[93]  D. Keppler,et al.  Characterization of the ATP-dependent leukotriene C4 export carrier in mastocytoma cells. , 1994, European journal of biochemistry.

[94]  D. Keppler,et al.  Characterization of the human multidrug resistance protein isoform MRP3 localized to the basolateral hepatocyte membrane , 1999, Hepatology.

[95]  S. Aaronson,et al.  Expression of multidrug resistance-associated protein in NIH/3T3 cells confers multidrug resistance associated with increased drug efflux and altered intracellular drug distribution. , 1995, Cancer research.

[96]  M. Kool,et al.  A mutation in the human canalicular multispecific organic anion transporter gene causes the Dubin‐Johnson syndrome , 1997, Hepatology.

[97]  J. Foekens,et al.  Multidrug resistance protein in recurrent breast cancer , 1997, The Lancet.

[98]  Y. Maehara,et al.  Multidrug resistance‐associated protein expression in clinical gastric carcinoma , 1996, Cancer.

[99]  K. Ono,et al.  ATP-Dependent efflux of CPT-11 and SN-38 by the multidrug resistance protein (MRP) and its inhibition by PAK-104P. , 1999, Molecular pharmacology.

[100]  F. Bosman,et al.  Expression of the multidrug resistance protein (MRP) in squamous cell carcinoma of the oesophagus and response to pre-operative chemotherapy. , 1998, European journal of cancer.

[101]  J. Baak,et al.  Early multidrug resistance, defined by changes in intracellular doxorubicin distribution, independent of P-glycoprotein. , 1991, British Journal of Cancer.

[102]  D. Hipfner,et al.  Immunohistochemical detection of multidrug resistance protein in human lung cancer and normal lung. , 1998, Clinical cancer research : an official journal of the American Association for Cancer Research.

[103]  D. Marquardt,et al.  Mechanisms of multidrug resistance in HL60 cells: detection of resistance-associated proteins with antibodies against synthetic peptides that correspond to the deduced sequence of P-glycoprotein. , 1990, Cancer research.

[104]  S. Cole,et al.  Multidrug resistance-associated protein: sequence correction. , 1993, Science.

[105]  L. Kasturi,et al.  The Amino Acid at the X Position of an Asn-X-Ser Sequon Is an Important Determinant of N-Linked Core-glycosylation Efficiency (*) , 1996, The Journal of Biological Chemistry.

[106]  D. Hipfner,et al.  Pharmacological characterization of the murine and human orthologs of multidrug-resistance protein in transfected human embryonic kidney cells. , 1997, Molecular pharmacology.

[107]  D. Hipfner,et al.  Expression of multidrug resistance-associated protein (MRP), MDR1 and DNA topoisomerase II in human multidrug-resistant bladder cancer cell lines. , 1995, British Journal of Cancer.

[108]  W. Lehmann,et al.  Multidrug resistance protein-mediated transport of chlorambucil and melphalan conjugated to glutathione. , 1998, British Journal of Cancer.

[109]  D. Hipfner,et al.  Location of a protease-hypersensitive region in the multidrug resistance protein (MRP) by mapping of the epitope of MRP-specific monoclonal antibody QCRL-1. , 1996, Cancer research.

[110]  T. Ishikawa,et al.  Transient induction of the MRP/GS-X pump and gamma-glutamylcysteine synthetase by 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3- nitrosourea in human glioma cells. , 1997, Cancer research.

[111]  W. Wilson,et al.  Expression of the Multidrug Resistance-Associated Protein Gene in Refractory Lymphoma: Quantitation by a Validated Polymerase Chain Reaction Assay , 1997 .

[112]  T. Ishikawa,et al.  The ATP-dependent glutathione S-conjugate export pump. , 1992, Trends in biochemical sciences.

[113]  M. Mutoh,et al.  Reversal of heavy metal resistance in multidrug-resistant human KB carcinoma cells. , 1997, Biochemical and biophysical research communications.

[114]  N. Mulder,et al.  Transport of glutathione conjugates into secretory vesicles is mediated by the multidrug‐resistance protein 1 , 1998, International journal of cancer.

[115]  D. Hipfner,et al.  Membrane Topology of the Multidrug Resistance Protein (MRP) , 1997, The Journal of Biological Chemistry.

[116]  J. Walker,et al.  Distantly related sequences in the alpha‐ and beta‐subunits of ATP synthase, myosin, kinases and other ATP‐requiring enzymes and a common nucleotide binding fold. , 1982, The EMBO journal.

[117]  A. Townsend,et al.  Multidrug resistance protein and glutathione S-transferase P1-1 act in synergy to confer protection from 4-nitroquinoline 1-oxide toxicity. , 1998, Carcinogenesis.

[118]  J. Riordan,et al.  Stimulation of ATPase Activity of Purified Multidrug Resistance-associated Protein by Nucleoside Diphosphates* , 1998, The Journal of Biological Chemistry.

[119]  P. Jansen,et al.  ATP‐ and glutathione‐dependent transport of chemotherapeutic drugs by the multidrug resistance protein MRP1 , 1999, British journal of pharmacology.

[120]  M. Center,et al.  Adriamycin resistance in HL60 cells in the absence of detectable P-glycoprotein. , 1987, Biochemical and biophysical research communications.

[121]  I. Pastan,et al.  Biochemistry of multidrug resistance mediated by the multidrug transporter. , 1993, Annual review of biochemistry.

[122]  S. Cole,et al.  Characterization of vincristine transport by the M(r) 190,000 multidrug resistance protein (MRP): evidence for cotransport with reduced glutathione. , 1998, Cancer research.

[123]  Kevin D. Raney,et al.  DNA adduction by the potent carcinogen aflatoxin B1 : mechanistic studies , 1994 .

[124]  J. Bryan,et al.  The ABCs of ATP-sensitive potassium channels: more pieces of the puzzle. , 1997, Current opinion in cell biology.

[125]  K. Ueda,et al.  Anti‐cancer drugs and glutathione stimulate vanadate‐induced trapping of nucleotide in multidrug resistance‐associated protein (MRP) , 1997, FEBS letters.

[126]  D. Meijer,et al.  Hepatobiliary secretion of organic compounds; molecular mechanisms of membrane transport. , 1995, Biochimica et biophysica acta.

[127]  M. Pinkoski,et al.  Elevated expression of annexin II (lipocortin II, p36) in a multidrug resistant small cell lung cancer cell line. , 1992, British Journal of Cancer.

[128]  S. Levy,et al.  Active efflux of the free acid form of the fluorescent dye 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein in multidrug-resistance-protein-overexpressing murine and human leukemia cells. , 1997, European journal of biochemistry.

[129]  M. Slovak,et al.  Localization of a novel multidrug resistance-associated gene in the HT1080/DR4 and H69AR human tumor cell lines. , 1993, Cancer research.

[130]  S. Cole,et al.  ATPase activity of purified and reconstituted multidrug resistance protein MRP1 from drug-selected H69AR cells. , 1999, Biochimica et biophysica acta.

[131]  J. Endicott,et al.  The biochemistry of P-glycoprotein-mediated multidrug resistance. , 1989, Annual review of biochemistry.

[132]  S. Mirski,et al.  Alterations in glutathione and glutathione-related enzymes in a multidrug-resistant small cell lung cancer cell line. , 1990, Molecular pharmacology.

[133]  C. Meijer,et al.  Immunochemical detection of the multidrug resistance-associated protein MRP in human multidrug-resistant tumor cells by monoclonal antibodies. , 1994, Cancer research.

[134]  J. Lupski,et al.  A photoreceptor cell-specific ATP-binding transporter gene (ABCR) is mutated in recessive Starqardt macular dystrophy , 1997, Nature Genetics.

[135]  R. Scheper,et al.  Regulation by glutathione of drug transport in multidrug-resistant human lung tumour cell lines overexpressing multidrug resistance-associated protein. , 1995, British Journal of Cancer.

[136]  P. Gros,et al.  Topology Mapping of the Amino-terminal Half of Multidrug Resistance-associated Protein by Epitope Insertion and Immunofluorescence* , 1997, The Journal of Biological Chemistry.

[137]  J. Riordan,et al.  ATPase Activity of Purified Multidrug Resistance-associated Protein* , 1997, The Journal of Biological Chemistry.

[138]  G. Dekan,et al.  Expression of the multidrug resistance-associated protein (MRP) gene in colorectal carcinomas. , 1997, British Journal of Cancer.

[139]  K. Ueda,et al.  How does P-glycoprotein recognize its substrates? , 1997, Seminars in cancer biology.

[140]  A. Townsend,et al.  Coordinated Action of Glutathione S-Transferases (GSTs) and Multidrug Resistance Protein 1 (MRP1) in Antineoplastic Drug Detoxification , 1998, The Journal of Biological Chemistry.

[141]  E Schneider,et al.  ATP-binding-cassette (ABC) transport systems: functional and structural aspects of the ATP-hydrolyzing subunits/domains. , 1998, FEMS microbiology reviews.

[142]  W. Berger,et al.  Expression of the multidrug resistance‐associated protein (MRP) and chemoresistance of human non‐small‐cell lung cancer cells , 1997 .

[143]  A. Guhlmann,et al.  Hereditary defect of hepatobiliary cysteinyl leukotriene elimination in mutant rats with defective hepatic anion excretion , 1987, Hepatology.

[144]  K. Kohno,et al.  Overexpression of Multidrug Resistance Protein Gene in Human Cancer Cell Lines Selected for Drug Resistance to Epipodophyllotoxins , 1996, Japanese journal of cancer research : Gann.

[145]  M. Haber,et al.  Expression of the multidrug resistance-associated protein (MRP) gene correlates with amplification and overexpression of the N-myc oncogene in childhood neuroblastoma. , 1994, Cancer research.

[146]  D. Hipfner,et al.  Overexpression of multidrug resistance-associated protein (MRP) increases resistance to natural product drugs. , 1994, Cancer research.

[147]  N. Dean,et al.  Reduction of expression of the multidrug resistance protein (MRP) in human tumor cells by antisense phosphorothioate oligonucleotides. , 1996, Biochemical pharmacology.

[148]  T. Ishikawa,et al.  ATP-dependent primary active transport of cysteinyl leukotrienes across liver canalicular membrane. Role of the ATP-dependent transport system for glutathione S-conjugates. , 1990, The Journal of biological chemistry.

[149]  D. Hipfner,et al.  Characterization of the Mr 190,000 Multidrug Resistance Protein (MRP) in Drug-selected and Transfected Human Tumor Cells , 1995 .

[150]  M. Kool,et al.  Analysis of expression of cMOAT (MRP2), MRP3, MRP4, and MRP5, homologues of the multidrug resistance-associated protein gene (MRP1), in human cancer cell lines. , 1997, Cancer research.