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Multidrug Resistance Associated with Overexpression of MRP

  • Chapter
Drug Resistance

Part of the book series: Cancer Treatment and Research ((CTAR,volume 87))

Abstract

Drug resistance occurs with all classes of chemotherapeutic agents and is a major cause of treatment failure in many human malignancies. In some types of tumors, such as non-small cell lung carcinomas, this resistance is inherent, while in others (e.g., acute myelogenous leukemia) it is acquired during treatment. The problem of drug resistance has been studied in the laboratory primarily by using drug-selected, cultured tumor cell lines as model systems. These cell lines are typically derived by exposure of cells to a single chemotherapeutic agent. When the selecting drug is a natural product, the resistant cells frequently acquire simultaneous crossresistance to structurally unrelated compounds that exert their cytotoxicity through a number of different subcellular targets. Such cells are commonly referred to as displaying a multidrug resistance phenotype. The spectrum of drugs encompassed by this experimental phenotype are almost always natural products and their semisynthetic derivatives, and they include agents such as VP-16 (etoposide), doxorubicin, mitoxantrone, and vincristine. Since many of these drugs are therapeutically very useful, elucidation of the mechanisms responsible for causing resistance to these agents is of considerable interest and potential clinical importance.

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References

  1. Ueda K, Cardarelli C, Gottesman MM, Pastan I (1987) Expression of a full-length cDNA for the human “MDR1” gene confers resistance to colchicine, doxorubicin, and vinblastine. Proc Natl Acad Sci USA 84:3004–3008.

    Article  PubMed  CAS  Google Scholar 

  2. Gros P, Neriah YB, Croop JM, Housman DE (1986) Isolation and expression of a complementary DNA that confers multidrug resistance. Nature 323:728–731.

    Article  PubMed  CAS  Google Scholar 

  3. Cole SPC, Bhardwaj G, Gerlach JH, Mackie JE, Grant CE, Almquist KC, Stewart AJ, Kurz EU, Duncan AMV, Deeley RG (1992) Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line. Science 258:1650–1654.

    Article  PubMed  CAS  Google Scholar 

  4. Cole SPC, Deeley RG (1993) Multidrug resistance-associated protein: Sequence correction. Science 260:879.

    Article  PubMed  CAS  Google Scholar 

  5. Grant CE, Valdimarsson G, Hipfner DR, Almquist KC, Cole SPC, Deeley RG (1994) Overexpression of multidrug resistance-associated protein (MRP) increases resistance to natural product drugs. Cancer Res 54:357–361.

    PubMed  CAS  Google Scholar 

  6. Krishnamachary N, Center MS (1993) The MRP gene associated with a non-P-glycoprotein multidrug resistance encodes a 190-kDa membrane bound glycoprotein. Cancer Res 53:3658–3661.

    PubMed  CAS  Google Scholar 

  7. Juliano RL, Ling V (1976) A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants. Biochim Biophys Acta 455:152–162.

    Article  PubMed  CAS  Google Scholar 

  8. Bradley G, Juranka PF, Ling V (1988) Mechanism of multidrug resistance. Biochim Biophys Acta 948:87–128.

    PubMed  CAS  Google Scholar 

  9. Gerlach JH, Kartner N, Bell DR, Ling V (1986) Multidrug resistance. Cancer Surv 5:25–46.

    PubMed  CAS  Google Scholar 

  10. Gottesman MM, Pastan I (1988) The multidrug transporter, a double-edged sword. J Biol Chem 263:12163–12166.

    PubMed  CAS  Google Scholar 

  11. Juranka PF, Zastawny RL, Ling V (1989) P-glycoprotein: Multidrug-resistance and a superfamily of membrane-associated transport proteins. FASEB J 3:2583–2592.

    PubMed  CAS  Google Scholar 

  12. Georges E, Sharom FJ, Ling V (1990) Multidrug resistance and chemosensitization: Therapeutic implications for cancer chemotherapy. Adv Pharmacol 21:185–220.

    Article  PubMed  CAS  Google Scholar 

  13. Roninson IB (1992) From amplification to function: The case of the MDRI gene. Muta Res 276:151–161.

    CAS  Google Scholar 

  14. Tsuruo T (1988) Mechanisms of multidrug resistance and implications for therapy. Jpn J Cancer Res 79:285–296.

    PubMed  CAS  Google Scholar 

  15. Endicott JA, Ling V (1989) The biochemistry of P-glycoprotein-mediated multidrug resistance. Annu Rev Biochem 58:137–171.

    Article  PubMed  CAS  Google Scholar 

  16. Gerlach JH (1989) Structure and function of P-glycoprotein. In RF Ozols, ed. Drug Resistance in Cancer Therapy. Boston: Kluwer Academic, pp 37–53.

    Chapter  Google Scholar 

  17. Gottesman MM, Pastan I (1993) Biochemistry of multidrug resistance mediated by the multidrug transporter. Annu Rev Biochem 62:385–427.

    Article  PubMed  CAS  Google Scholar 

  18. Chin K-V, Pastan I, Gottesman MM (1993) Function and regulation of the human multidrug resistance gene. Adv Cancer Res 60:157–180.

    Article  PubMed  CAS  Google Scholar 

  19. Leveill-Webster CR, Arias IM (1995) The biology of the P-glycoproteins. J Membr Biol 143:89–102.

    Google Scholar 

  20. Goldstein LJ, Galski H, Fojo A, Willingham M, Lai S-L, Gazdar A, Pirker R, Green A, Crist W, Brodeur GM, Lieber M, Cossman J, Gottesman MM, Pastan I (1989) Experession of a multidrug resistance gene in human cancers. J Natl Cancer Inst 81:116–124.

    Article  PubMed  CAS  Google Scholar 

  21. Lai S-L, Goldstein LJ, Gottesman MM, Pastan I, Tsai C-M, Johnson BE, Mulshine JL, Ihde DC, Kayser K, Gazdar AF (1989) MDR1 gene expression in lung cancer. J Natl Cancer Inst 81:1144–1150.

    Article  PubMed  CAS  Google Scholar 

  22. Mirski SEL, Gerlach JH, Cole SPC (1987) Multidrug resistance in a human small cell lung cancer cell line selected in adriamycin. Cancer Res 47:2594–2598.

    PubMed  CAS  Google Scholar 

  23. McGrath T, Center MS (1987) Adriamycin resistance in HL60 cells in the absence of detectable P-glycoprotein. Biochem Biophys Res Commun 145:1171–1176.

    Article  PubMed  CAS  Google Scholar 

  24. Slovak ML, Hoeltge GA, Dalton WS, Trent JM (1988) Pharmacological and biological evidence for differing mechanisms of doxorubicin resistance in two human tumor cell lines. Cancer Res 48:2793–2797.

    PubMed  CAS  Google Scholar 

  25. de Jong S, Zijlstra JG, de Vries EGE, Mulder NH (1990) Reduced DNA topoisomerase II activity and drug-induced DNA cleavage activity in an Adriamycin-resistant human small cell lung carcinoma cell line. Cancer Res 50:304–309.

    PubMed  Google Scholar 

  26. Reeve JG, Rabbitts PH, Twentyman PR (1990) Non-P-glycoprotein-mediated multidrug resistance with reduced EGF receptor expression in a human large cell lung cancer cell line. Br J Cancer 61:851–855.

    Article  PubMed  CAS  Google Scholar 

  27. Cole SPC (1992) The 1991 Merck Frosst Award. Multidrug resistance in small cell lung cancer. Can J Physiol Pharmacol 70:313–329.

    Article  PubMed  CAS  Google Scholar 

  28. Hill BT (1993) Differing patterns of cross-resistance resulting from exposures to specific antitumour drugs or to radiation in vitro. Cytotechnology 12:265–288.

    Article  PubMed  CAS  Google Scholar 

  29. Ferguson PJ, Fisher MH, Stephenson J, Li D-H, Zhou B-S, Cheng Y-C (1988) Combined modalities of resistance in etoposide-resistant human KB cell lines. Cancer Res 48:5956–5964.

    PubMed  CAS  Google Scholar 

  30. Eijdems EWH, Borst P, Jongsma APM, de Jong S, de Vries EGE, van Groenigen M, Versantvoort CHM, Nieuwint AWM, Baas F (1992) Genetic transfer of non-P-glycoprotein-mediated multidrug resistance (MDR) in somatic cell fusion: Dissection of a compound MDR phenotype. Proc Natl Acad Sci USA 89:3498–3502.

    Article  PubMed  CAS  Google Scholar 

  31. Cole SPC (1986) Rapid chemosensitivity testing of human lung tumor cells using the MTT assay. Cancer Chemother Pharmacol 17:259–263.

    Article  PubMed  CAS  Google Scholar 

  32. Gazdar AF, Carney DN, Russell EK, Sims HL, Baylin SB, Bunn PA, Guccion JG, Minna JD (1980) Establishment of continuous, clonable cultures of small-cell carcinoma of the lung which have amine precursor uptake and decarboxylation cell properties. Cancer Res 40:3502–3507.

    PubMed  CAS  Google Scholar 

  33. Cole SPC, Chanda ER, Dicke FP, Gerlach JH, Mirski SEL (1991) Non-P-glycoprotein-mediated multidrug resistance in a small cell lung cancer cell line: Evidence for decreased susceptibility to drug-induced DNA damage and reduced levels of topoisomerase II. Cancer Res 51:3345–3352.

    PubMed  CAS  Google Scholar 

  34. Evans CD, Mirski SEL, Danks MK, Cole SPC (1994) Reduced levels of topoisomerase II a and β in a multidrug resistant small cell lung cancer cell line. Cancer Chemother Pharmacol 34:242–248.

    Article  PubMed  CAS  Google Scholar 

  35. Cole SPC, Downes HF, Mirski SEL, Clements DJ (1990) Alterations in glutathione and glu-tathione-related enzymes in a multidrug resistant small cell lung cancer cell line. Mol Pharmacol 37:192–197.

    PubMed  CAS  Google Scholar 

  36. Cole SPC, Sparks KE, Fraser K, Loe DW, Grant CE, Wilson GM, Deeley RG (1994) Pharmacological characterization of multidrug resistant MRP-transfected human tumor cells. Cancer Res 54:5902–5910.

    PubMed  CAS  Google Scholar 

  37. Kruh GD, Chan A, Myers K, Gaughan K, Miki T, Aaronson SA (1994) Expression complementary DNA library transfer establishes mrp as a multidrug resistance gene. Cancer Res 54:1649–1652.

    PubMed  CAS  Google Scholar 

  38. Zaman GJR, Flens MJ, Van Leusden MR, de Haas M, Mulder HS, Lankelma J, Pinedo HM, Scheper RJ, Baas F, Broxterman HJ, Borst P (1994) The human multidrug resistance-associated protein MRP is a plasma membrane drug-efflux pump. Proc Natl Acad Sci USA 91:8822–8826.

    Article  PubMed  CAS  Google Scholar 

  39. McGrath T, Latoud C, Arnold ST, Safa AR, Felsted RL, Canter MS (1989) Mechanisms of multidrug resistance in HL60 cells: Analysis of resistance associated membrane proteins and levels of mdr gene expression. Biochem Pharmacol 38:3611–3619.

    Article  PubMed  CAS  Google Scholar 

  40. Barrand MA, Rhodes T, Center MS, Twentyman PR (1993) Chemosensitisation and drug accumulation effects of cyclosporin A, PSC-833 and verapamil in human MDR large cell lung cancer cells expressing a 190 k membrane protein distinct from P-glycoprotein. Eur J Cancer 29:408–415.

    Article  Google Scholar 

  41. Zaman GJR, Versantvoort CHM, Smit JJM, Eijdems EWHM, de Haas M, Smith AJ, Broxterman HJ, Mulder NH, de Vries EGE, Baas F, Borst P (1993) Analysis of the expression of MRP, the gene for a new putative transmembrane drug transporter, in human multidrug resistant lung cancer cell lines. Cancer Res 53:1747–1750.

    PubMed  CAS  Google Scholar 

  42. Barrand MA, Heppell-Parton AC, Wright KA, Rabbitts PH, Twentyman PR (1994) A 190-kilodalton protein overexpressed in non-P-glycoprotein-containing multidrug-resistant cells and its relationship to the MRP gene. J Natl Cancer Inst 86:110–117.

    Article  PubMed  CAS  Google Scholar 

  43. Brock I, Hipfner DR, Nielsen BE, Jensen PB, Deeley RG, Cole SPC, Sehested M (1995) Sequential co-expression of the multidrug resistance genes, MRP and mdrl and their products in VP-16 (etoposide) selected H69 small cell lung cancer cells. Cancer Res 55:459–462.

    PubMed  CAS  Google Scholar 

  44. Binaschi M, Supino R, Gambetta RA, Giaccone G, Prosperi E, Capranico G, Cataldo I, Zunino F (1995) MRP gene overexpression is a human doxorubicin-resistant SCLC cell line: Alterations in cellular pharmacokinetics and in pattern of cross-resistance. Int J Cancer 61:1, 84–89.

    Article  Google Scholar 

  45. Slapak CA, Mizunuma N, Kufe DW (1994) Expression of the multidrug resistance associated protein and P-glycoprotein in doxorubicin-selected human myeloid leukemia cells. Blood 84:3113–3121.

    PubMed  CAS  Google Scholar 

  46. Davey RA, Longhurst TJ, Davey MW, Belov L, Harvie RM, Hancox D, Wheeler H (1995) Drug resistance mechanisms and MRP expression in response to epirubicin treatment in a human leukaemia cell line. Leuk Res 17:1–8.

    Google Scholar 

  47. Schneider E, Horton JK, Yang C-H, Nakagawa M, Cowan KH (1994) 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. Cancer Res 54:152–158.

    PubMed  CAS  Google Scholar 

  48. Benchekroun MN, Schneider E, Safa AR, Townsend AJ, Sinha BK (1994) Mechanisms of resistance to ansamycin antibiotics in human breast cancer cell lines. Mol Pharmacol 46:677–684.

    PubMed  CAS  Google Scholar 

  49. Hasegawa S, Abe T, Naito S, Kotoh S, Kumazawa J, Hipfner DR, Deeley RG, Cole SPC, Kuwano M (1995) Expression of multidrug resistance-associated protein (MRP), MDR1 and DNA topoisomerase II in human multidrug-resistant bladder cancer cell lines. Br J Cancer 71:907–913.

    Article  PubMed  CAS  Google Scholar 

  50. Tasaki Y, Nakagawa M, Ogata J, Kiue A, Tanimura H, Kuwano M, Nomura Y (1995) Reversal by a dihydropyridine derivative of non-P-glycoprotein-mediated multidrug resistance in etoposide-resistant human prostatic cancer cell lines. J Urol, 154:1210–1216.

    Article  PubMed  CAS  Google Scholar 

  51. Sumizawa T, Chuman Y, Sakamoto H, Iemura K, Almquist KC, Deeley RG, Cole SPC, Akiyama S-I (1994) Non-P-glycoprotein-mediated multidrug resistant human KB cells selected in medium containing Adriamycin, cepharanthine and mezerein. Soma Cell Mol Genet 20:423–435.

    Article  CAS  Google Scholar 

  52. Gaj CL, Anyanwutaku IO, Cole SC, Chang Y, Cheng YC (1995) Reversal of multidrug resistance associated protein mediated multidrug resistance in a human carcinoma cell line by the 1/-enantiomer of verapamil (abstr). Proc Am Assoc Cancer Res 36:346.

    Google Scholar 

  53. Slovak ML, Ho JP, Bhardwaj G, Kurz EU, Deeley RG, Cole SPC (1993) Localization of a novel multidrug resistance-associated gene in the HT1080/DR4 and H69AR human tumor cell lines. Cancer Res 53:3221–3225.

    PubMed  CAS  Google Scholar 

  54. Slapak CA, Fracasso PM, Martell RL, Toppmeyer DL, Lecerf J-M, Levy SB (1994) Overexpression of the multidrug resistance-associated protein (MRP) gene in vincristine but not doxorubicin-selected multidrug resistant murine erythroleukemia cells. Cancer Res 54:5607–5613.

    PubMed  CAS  Google Scholar 

  55. Abe T, Hasegawa S, Taniguchi K, Yokomizo A, Kuwano T, Ono M, Mori T, Hori S, Kohno K, Kuwano M (1994) Possible involvement of multi drug-resistance-associated protein (MRP) gene expression in spontaneous drug resistance to vincristine, etoposide and adriamycin in human glioma cells. Int J Cancer 58:860–864.

    Article  PubMed  CAS  Google Scholar 

  56. Bordow SB, Haber M, Madafiglio J, Cheung B, Marshall GM, Norris MD (1994) Expression of the multidrug resistance-associated protein (MRP) gene correlates with amplification and overexpression of the N-myc oncogene in childhood neuroblastoma. Cancer Res 54:5036–5040.

    PubMed  CAS  Google Scholar 

  57. Sugawara I, Arai T, Yamashita T, Yoshida A, Masunaga S, Itoyama S (1994) Expression of multidrug resistance-associated protein (MRP) in anaplastic carcinoma of the thyroid. Cancer Lett 82:185–188.

    Article  PubMed  CAS  Google Scholar 

  58. Abe T, Koike K, Ohga T, Kubo T, Wada M, Kohno K, Mori T, Hidaka K, Kuwano M (1995) Chemosensitization of spontaneous multidrug resistance by a 1,4-dihydropyridine analog and verapamil in human glioma cell lines overexpressing MRP or MDR1. Br J Cancer 72:418–423.

    Article  PubMed  CAS  Google Scholar 

  59. Higgins CF (1992) ABC transporters: From microorganisms to man. Ann Rev Cell Biol 8:67–113.

    Article  PubMed  CAS  Google Scholar 

  60. Fath MJ, Kolter R (1993) ABC transporters: Bacterial exporters. Microbiol Rev 57:995–1017.

    PubMed  CAS  Google Scholar 

  61. Riordan JR, Rommens JM, Kerem B-S, Alon N, Rozmahel R, Grzelczak Z, Zielenski J, Lok S, Plasvsic N, Chou J-L, Drumm ML, Iannuzzi MC, Collins FS, Tsui L-C (1989) Identification of the cystic fibrosis gene: Cloning and characterization of complementary DNA. Science 245:1066–1073.

    Article  PubMed  CAS  Google Scholar 

  62. Welsh MJ, Smith AE (1993) Molecular mechanisms of CFTR chloride channel dysfunction in cystic fibrosis. Cell 73:1251–1254.

    Article  PubMed  CAS  Google Scholar 

  63. Kelly A, Powis SH, Kerr L-A, Mockridge I, Elliott T, Bastin J, Uchanska-Ziegler B, Ziegler A, Trowsdale J, Townsend A (1992) Assembly and function of the two ABC transporter proteins encoded in the human major histocompatibility complex. Nature 355:641–644.

    Article  PubMed  CAS  Google Scholar 

  64. Neefjes JJ, Momburg F, Hammerling GJ (1993) Selective and ATP-dependent translocation of peptides by the МНC-encoded transporter. Science 261:769–771.

    Article  PubMed  CAS  Google Scholar 

  65. Heemels M-T, Schumacher TNM, Wonigeit K, Ploegh HL (1993) Peptide translocation by variants of the transporter associated with antigen processing. Science 262:2059–2063.

    Article  PubMed  CAS  Google Scholar 

  66. Almquist KC, Loe DW, Hipfner DR, Mackie JE, Cole SPC, Deeley RG (1995) Characterization of the 190kDa multidrug resistance protein (MRP) in drug-selected and transfected human tumor cells. Cancer Res 55:102–110.

    PubMed  CAS  Google Scholar 

  67. Jones DT, Taylor WR, Thornton JM (1994) A model recognition approach to the prediction of all-helical membrane protein structure and topology. Biochemistry 33:3038–3049.

    Article  PubMed  CAS  Google Scholar 

  68. Stride BD, Valdimarsson G, Gerlach JH, Wilson G, Cole SPC, Deeley RG (1996) Structure and expression of the mRNA encoding the murine multidrug resistance protein (MRP), an ATP-binding cassette transporter. Mol Pharmacol, in press.

    Google Scholar 

  69. Yoshimura A, Kuwazuru Y, Sumizawa T, Ichikawa M, Ikeda S-I, Uda T, Akiyama S-I (1989) Cytoplasmic orientation and two-domain structure of the multidrug transporter, P-glycoprotein, demonstrated with sequence-specific antibodies. J Biol Chem 264:16282–16291.

    PubMed  CAS  Google Scholar 

  70. Georges E, Tsuruo T, Ling V (1993) Topology of P-glycoprotein as determined by epitope mapping of MRK-16 monoclonal antibody. J Biol Chem 268:1792–1798.

    PubMed  CAS  Google Scholar 

  71. Georges E, Bradley G, Gariepy J, Ling V (1990) Detection of P-glycoprotein isoforms by gene-specific monoclonal antibodies. Proc Natl Acad Sci USA 87:152–156.

    Article  PubMed  CAS  Google Scholar 

  72. Skach WR, Lingappa VR (1994) Transmembrane orientation and topogenesis of the third and fourth membrane-spanning regions of human P-glycoprotein (MDR1). Cancer Res 54:3202–3209.

    PubMed  CAS  Google Scholar 

  73. Skach WR, Calayag MC, Lingappa VR (1993) Evidence for an alternate model of human P-glycoprotein structure and biogenesis. J Biol Chem 268:6903–6908.

    PubMed  CAS  Google Scholar 

  74. Zhang J-T, Ling V (1991) Study of membrane orientation and glycosylated extracellular loops of mouse P-glycoprotein by in vitro translation. J Biol Chem 266:18224–18232.

    PubMed  CAS  Google Scholar 

  75. Zhang J-T, Lee CH, Duthie M, Ling V (1995) Topological determinants of internal transmembrane segments in P-glycoprotein sequences. J Biol Chem 270:1742–1746.

    Article  PubMed  CAS  Google Scholar 

  76. Callahan HL, Beverley SM (1991) Heavy metal resistance: A new role for P-glycoproteins in Leishmania. J Biol Chem 266:18427–18430.

    PubMed  CAS  Google Scholar 

  77. Papadopoulou B, Roy G, Dey S, Rosen BP, Ouellette M (1994) Contribution of the Leishmania P-glycoprotein-related gene ItpgpA to oxyanion resistance. J Biol Chem 269:11980–11986.

    PubMed  CAS  Google Scholar 

  78. Szczypka MS, Wemmie JA, Moye-Rowley WS, Thiele DJ (1994) A yeast metal resistance protein similar to human cystic fibrosis transmembrane conductance regulator (CFTR) and multidrug resistance-associated protein. J Biol Chem 269:22853–22857.

    PubMed  CAS  Google Scholar 

  79. Aguilar-Bryan L, Nichols CG, Wechsler SW, Clement JP, Boyd AE, Gonzalez G, Herrera-Sosa H, Nguy K, Bryan J, Nelson DA (1995) Cloning of the β cell high-affinity sulfonylurea receptor: A regulator of insulin secretion. Science 268:423–426.

    Article  PubMed  CAS  Google Scholar 

  80. Walker JE, Saraste M, Runswick MJ, Gay NJ (1982) Distantly related sequences in the a- and ß-subunits of ATP synthase, myosin, kinases and other ATP-requiring enzymes and a common nucleotide binding fold. EMBO J 1:945–951.

    PubMed  CAS  Google Scholar 

  81. Ma L, Krishnamachary N, Cnter MS (1995) Phosphorylation of the multidrug resistance associated protein gene encoded protein P190. Biochemistry 34:3338–3343.

    Article  PubMed  CAS  Google Scholar 

  82. Lis H, Sharon N (1993) Protein glycosylation. Structural and functional aspects. Eur J Biochem 218:1–27.

    Article  PubMed  CAS  Google Scholar 

  83. Becq F, Jensen TJ, Chang X-B, Savoia A, Rommens JM, Tsui L-C, Buchwald M, Riordan JR, Hanrahan JW (1994) Phosphatase inhibitors activate normal and defective CFTR chloride channels. Proc Natl Acad Sci USA 91:9160–9164.

    Article  PubMed  CAS  Google Scholar 

  84. Chambers TC, Pohl J, Ryanor RL, Kuo JF (1993) Identification of specific sites in human P-glycoprotein phosphorylated by protein kinase C. J Biol Chem 268:4592–4595.

    PubMed  CAS  Google Scholar 

  85. Orr GA, Han EK-H, Browne PC, Nieves E, O’Connor BM, Yang C-PH, Horwitz SB (1993) Identification of the major phosphorylation domain of murine mdr1b P-glycoprotein. Analysis of the protein kinase A and protein kinase C phosphorylation sites. J Biol Chem 268:5054–25062.

    Google Scholar 

  86. Picciotto MR, Cohn JA, Bertuzzi G, Greengard P, Nairn AC (1992) Phosphorylation of the cystic fibrosis transmembrane conductance regulator. J Biol Chem 267:12742–12752.

    PubMed  CAS  Google Scholar 

  87. Chang X-B, Tabcharani JA, Hou Y-X, Jensen TJ, Kartner N, Alon N, Hanrahan JW, Riordan JR (1993) Protein kinase A (PKA) still activates CFTR chloride channel after mutagenesis of all 10 PKA consensus phosphorylation sites. J Biol Chem 268:11304–11311.

    PubMed  CAS  Google Scholar 

  88. Cheng SH, Rich DP, Marshall J, Gregory RJ, Welsh MJ, Smith AE (1991) Phosphorylation of the R domain by cAMP-dependent protein kinase regulates the CFTR chloride channel. Cell 66:1027–1036.

    Article  PubMed  CAS  Google Scholar 

  89. Chambers TC, Zheng B, Kuo JF (1992) Regulation of phorbol ester and protein kinase C inhibitors, and by a protein phosphatase inhibitor (okadaic acid), of P-glycoprotein phosphorylation and relationship to drug accumulation in multidrug-resistant human KB cells. Mol Pharmacol 41:1008–1015.

    PubMed  CAS  Google Scholar 

  90. Bates SE, Lee JS, Dickstein B, Spolyar M, Fojo AT (1993) Differential modulation of P-glycoprotein transport by protein kinase inhibition. Biochemistry 32:9156–9164.

    Article  PubMed  CAS  Google Scholar 

  91. Sato W, Yusa K, Naito M, Tsuruo T (1990) Staurosporine, a potent inhibitor of C-kinase, enhances drug accumulation in multidrug-resistant cells. Biochem Biophys Res Commun 173:1252–1257.

    Article  PubMed  CAS  Google Scholar 

  92. Sampson KE, Wolf CL, Abraham I (1993) Staurosporine reduces P-glycoprotein expression and modulates resistance. Cancer Lett 68:7–14.

    Article  PubMed  CAS  Google Scholar 

  93. Epand RM, Stafford AR (1993) Protein kinases and multidrug resistance. Cancer J 6:154–158.

    CAS  Google Scholar 

  94. Kuss BJ, Deeley RG, Cole SPC, Willman CL, Kopecky KJ, Wolman SR, Eyre HJ, Lane SA, Nancarrow JK, Whitmore SA, Callen DF (1994) Deletion of gene for multidrug resistance in acute myeloid leukaemia with inversion in chromosome 16: Prognostic implications. Lancet 343:1531–1534.

    Article  PubMed  CAS  Google Scholar 

  95. Eijems EWHM, de Haas M, Coco-Martin JM, Ottenheim CPE, Zaman GJR, Dauwerse GH, Breuning MH, Twentyman PR, Borst P, Baas F (1995) Mechanisms of MRP over-expression in four human lung-cancer cell lines and analysis of the MRP amplicon. Int J Cancer 60:676–684.

    Article  Google Scholar 

  96. Ray ME, Guan X-Y, Slovak ML, Trent JM, Meltzer PS (1994) Rapid detection, cloning and molecular cytogenetic characterisation of sequences from an MRP-encoding amplicon by chromosome microdissection. Br J Cancer 70:85–90.

    Article  PubMed  CAS  Google Scholar 

  97. Slovak ML, Ho J, Deeley RG, Cole SPC, de Vries EGE, Broxterman H, Scheffer GL, Scheper RJ (1995) The drug resistance related protein LRP maps proximal to MRP on the short arm of chromosome 16 (abstr). Proc Am Assoc Cancer Res 36:114.

    Google Scholar 

  98. Shen D-W, Fojo A, Chin JE, Roninson IB, Richert N, Pastan I, Gottesman MM (1986) Human multidrug-resistant cell lines: Increased mdr1 expression can precede gene amplification. Science 232:643–645.

    Article  PubMed  CAS  Google Scholar 

  99. Baas F, Jongsma APM, Broxterman HJ, Arceci RJ, Housman D, Scheffer GL, Riethorst A, van Groenigen M, Nieuwint AWM, Joenje H (1990) Non-P-glycoprotein mediated mechanism for multidrug resistance precedes P-glycoprotein expression during in vitro selection for doxorubicin resistance in a human lung cancer cell line. Cancer Res 50:5392–5398.

    PubMed  CAS  Google Scholar 

  100. Zhu Q, Center MS (1994) Cloning and sequence analysis of the promoter region of the MRP gene of HL60 cells isolated for resistance to Adriamycin. Cancer Res 54:4488–4492.

    PubMed  CAS  Google Scholar 

  101. Kurz EU, Grant CE, Vasa MZ, Burtch-Wright RA, Cole SPC, Deeley RG (1995) Analysis of the proximal promoter region of the multidrug resistance protein (MRP) gene in three small cell lung cancer cell lines (abstr). Proc Am Assoc Cancer Res 36:1917.

    Google Scholar 

  102. Ueda K, Pastan I, Gottesman MM (1987) Isolation and sequence of the promoter region of the human multidrug-resistance (P-glycoprotein) gene. J Biol Chem 262:17432–17436.

    PubMed  CAS  Google Scholar 

  103. Dynan WS, Tjian R (1985) Control of eukaryotic messenger RNA synthesis by sequence-specific DNA-binding proteins. Nature 316:774–778.

    Article  PubMed  CAS  Google Scholar 

  104. Kohno K, Sato S-I, Uchiumi T, Takano H, Tanimura H, Miyazaki M, Matsuo K-I, Hidaka K, Kuwano M (1992) Activation of the human multidrug resistance 1 (MDR1) gene promoter in response to inhibitors of DNA topoisomerases. Int J Oncol 1:73–77.

    PubMed  CAS  Google Scholar 

  105. Chaudhary PM, Roninson IB (1993) Induction of multidrug resistance in human cells by transient exposure to different chemotherapeutic drugs. J Natl Cancer Inst 85:632–639.

    Article  PubMed  CAS  Google Scholar 

  106. Uchiumi T, Kohno K, Tanimura H, Hidaka K, Asakuno K, Abe H, Uchida Y, Kuwano M (1993) Involvement of protein kinase in environmental stress-induced activation of human multidrug resistance 1 (MDR1) gene promoter. FEBS Lett 326:11–16.

    Article  PubMed  CAS  Google Scholar 

  107. Kohno K, Sato S-I, Takano H, Matsuo K-I, Kuwano M (1989) The direct activation of human multidrug resistance gene (MDR1) by anticancer agents. Biochem Biophys Res Commun 165:1415–1421.

    Article  PubMed  CAS  Google Scholar 

  108. Miyazaki M, Kohno K, Uchiumi T, Tanimura H, Matsuo K-I, Nasu M, Kuwano M (1992) Activation of human multidrug resistance-1 gene promoter in response to heat shock stress. Biochem Biophys Res Commun 187:677–684.

    Article  PubMed  CAS  Google Scholar 

  109. Tanimura H, Kohno K, Sato S-I, Uchiumi T, Miyazaki M, Kobayashi M, Kuwano M (1992) The human multidrug resistance 1 promoter has an element that responds to serum starvation. Biochem Biophys Res Commun 183:917–924.

    Article  PubMed  CAS  Google Scholar 

  110. Zastawny RL, Salvino R, Chen J, Benchimol S, Ling V (1993) The core promoter region of the P-glycoprotein gene is sufficient to confer differential responsiveness to wild-type and mutant p53. Oncogene 8:1529–1535.

    PubMed  CAS  Google Scholar 

  111. Chin K-V, Ueda K, Pastan I, Gottesman MM (1992) Modulation of activity of the promoter of the human MDR1 gene by ras and p53. Science 255:459–462.

    Article  PubMed  CAS  Google Scholar 

  112. Cornwell MM, Smith DE (1993) A signal transduction pathway for activation of the mdr1 promoter involves the proto-oncogene c-raf kinase. J Biol Chem 268:15347–15350.

    PubMed  CAS  Google Scholar 

  113. Cohen D, Piekarz RL, Hsu SI-H, DePinho RA, Carrasco N, Horwitz SB (1991) Structural and functional analysis of the mouse mdr1b gene promoter. J Biol Chem 266:2239–2244.

    PubMed  CAS  Google Scholar 

  114. Brown PC, Thorgeirsson SS, Silverman JA (1993) Cloning and regulation of the rat mdr2 gene. Nucleic Acids Res 21:3885–3891.

    Article  PubMed  CAS  Google Scholar 

  115. Hsu SI-H, Cohen D, Kirschner LS, Lothstein L, Hartstein M, Horwitz SB (1990) Structural analysis of the mouse mdr1a (P-glycoprotein) promoter reveals the basis for differential transcript heterogeneity in multidrug-resistant J774.2 cells. Mol Cell Biol 10:3596–3606.

    PubMed  CAS  Google Scholar 

  116. Raymond M, Gros P (1990) Cell-specific activity of cis-acting regulatory elements in the promoter of the mouse multidrug resistance gene mdr1. Mol Cell Biol 10:6036–6040.

    PubMed  CAS  Google Scholar 

  117. Safa AR, Glover CJ, Meyers MB, Biedler JL, Felsted RL (1986) Vinblastine photoaffinity labeling of a high molecular weight surface membrane glycoprotein specific for multidrug-resistant cells. J Biol Chem 261:6137–6140.

    PubMed  CAS  Google Scholar 

  118. Safa AR, Mehta ND, Agresti M (1989) Photoaffinity labeling of P-glycoprotein in multidrug resistant cells with photoactive analogs of colchicine. Biochem Biophys Res Commun 162:1402–1408.

    Article  PubMed  CAS  Google Scholar 

  119. Beck WT, Cirtain MC, Glover CJ, Felsted RL, Safa AR (1988) Effects of indole alkaloids on multidrug resistance and labeling of P-glycoprotein by a photoaffinity analog of vinblastine. Biochem Biophys Res Commun 153:959–966.

    Article  PubMed  CAS  Google Scholar 

  120. Busche R, Tümmler B, Riordan JR, Cano-Gauci DF (1989) Preparation and utility of a radioiodinated analogue of daunomycin in the study of multidrug resistance. Mol Pharmacol 35:414–421.

    PubMed  CAS  Google Scholar 

  121. Muller M, Meijer C, Zaman GJR, Borst P, Scheper RJ, Mulder NH, de Vries EGE, Jansen PLM (1994) Overexpression of the gene encoding the multidrug resistance-associated protein results in increased ATP-dependent glutathione S-conjugate transport. Proc Natl Acad Sci USA 91:13033–13037.

    Article  PubMed  CAS  Google Scholar 

  122. Shapiro AB, Ling V (1995) Using purified P-glycoprotein to understand multidrug resistance. J Bioenerg Biomenbr 27:7–13.

    Article  CAS  Google Scholar 

  123. Sharom FJ (1995) Characterization and functional reconstitution of the multidrug transporter. J Bioenerg Biomembr 27:15–22.

    Article  PubMed  CAS  Google Scholar 

  124. Coley HM, Workman P, Twentyman PR (1991) Retention of activity by selected anthracyclines in a multidrug resistant human large cell lung carcinoma line without P-glycoprotein hyperexpression. Br J Cancer 63:351–357.

    Article  PubMed  CAS  Google Scholar 

  125. McGrath T, Center MS (1988) Mechanisms of multidrug resistance in HL60 cells: Evidence that a surface membrane protein distinct from P-glycoprotein contributes to reduced cellular accumulation of drug. Cancer Res 48:3959–3963.

    PubMed  CAS  Google Scholar 

  126. Marsh W, Sicheri D, Center MS (1986) Isolation and characterization of adriamycin-resistant HL-60 cells which are not defective in the initial intracellular accumulation of drug. Cancer Res 46:4053–4057.

    PubMed  CAS  Google Scholar 

  127. Marquardt D, Center MS (1992) Drug transport mechanisms in HL60 cells isolated for resistance to adriamycin: Evidence for nuclear drug accumulation and redistribution in resistant cells. Cancer Res 52:3157–3163.

    PubMed  CAS  Google Scholar 

  128. Cole SPC (1992) Drug resistance and lung cancer. In J Wood, ed. Cancer: Concept to Clinic. Fairlawn, NJ: Medical Publishing Enterprises, pp 15–21.

    Google Scholar 

  129. Cole SPC, Bhardwaj G, Gerlach JH, Almquist KC, Deeley RG (1993) A novel ATP-binding cassette transporter gene overexpressed in multidrug-resistant human lung tumour cells (abstr). Proc Am Assoc Cancer Res 34:579.

    Google Scholar 

  130. Coley HM, Amos WB, Twentyman PR, Workman P (1993) Examination by laser scanning confocal fluorescence imaging microscopy of the subcellular localisation of anthracyclines in parent and multidrug resistant cell lines. Br J Cancer 67:1316–1323.

    Article  PubMed  CAS  Google Scholar 

  131. Gërvasoni JE Jr, Fields SZ, Krishna S, Baker MA, Rosado M Thuraisamy K, Hindenburg AA, Taub RN (1991) Subcellular distribution of daunorubicin in P-glycoprotein-positive and -negative drug-resistant cell Unes using laser-assisted confocal microscopy. Cancer Res 51:4955–4963.

    PubMed  Google Scholar 

  132. Hindenburg AA, Gervasoni JE Jr, Krishna S, Stewart VJ, Rosado M, Lutzky J, Bhalla K, Baker MA, Taub RN (1989) Intracellular distribution and pharmacokinetics of daunorubicin in anthracycline-sensitive and -resistant HL-60 cells. Cancer Res 49:4607–4614.

    PubMed  CAS  Google Scholar 

  133. Marquardt D, McCrone S, Center MS (1990) Mechanisms of multidrug resistance in HL60 cells: Detection of resistance-associated proteins with antibodies against synthetic peptides that correspond to the deduced squence of P-glycoprotein. Cancer Res 50:1426–1430.

    PubMed  CAS  Google Scholar 

  134. Flens MJ, Izquierdo MA, Scheffer GL, Fritz JM, Meijer CJLM, Scheper RJ, Zaman GJR (1994) Immunochemical detection of the multidrug resistance-associated protein MRP in human multidrug-resistant tumor cells by monoclonal antibodies. Cancer Res 54:4557–4563.

    PubMed  CAS  Google Scholar 

  135. Tew KD (1994) Glutathione-associated enzymes in anticancer drug resistance. Cancer Res 54:4313–4320.

    PubMed  CAS  Google Scholar 

  136. Abbaszadegan MR, Futscher BW, Klimecki WT, List A, Dalton WS (1994) Analysis of multidrug resistance-associated protein (MRP) messenger RNA in normal and malignant hematopoietic cells. Cancer Res 54:4676–4679.

    PubMed  CAS  Google Scholar 

  137. Leier I, Jedlitschky G, Buchholz U, Cole SPC, Deeley RG, Keppler D (1994) The MRP gene encodes an ATP-dependent export pump for leukotriene C4 and structurally related conjugates. J Biol Chem 269:27807–27810.

    PubMed  CAS  Google Scholar 

  138. Keppler D (1992) Leukotrienes: Biosynthesis, transport, inactivation and analysis. Rev Physiol Biochem Pharmacol 121:2–30.

    Google Scholar 

  139. Nicholson DW, Ali A, Vaillancourt JP, Calaycay JR, Mumford RA, Zamboni RJ, Ford-Hutchinson AW (1993) Purification to homogeneity and the N-terminal sequence of human leukotriene C4 synthase: A homodimeric glutathione 5-transferase composed of 18-kDa subunits. Proc Natl Acad Sci USA 90:2015–2019.

    Article  PubMed  CAS  Google Scholar 

  140. Combates NJ, Rzepka RW, Chen Y-NP, Cohen D (1994) NF-IL6, a member of the C/EBP family of transcription factors, binds and trans-activates the human MDR1 gene promoter. J Biol Chem 269:29715–29719.

    PubMed  CAS  Google Scholar 

  141. Ishikawa T (1992) The ATP-dependent glutathione S-conjugate export pump. Trends Biochem Sci 17:463–468.

    Article  PubMed  CAS  Google Scholar 

  142. Ishikawa T, Wright CD, Ishizuka H (1994) GS-X pump is functionally overexpressed in cis-diamminedichloroplatinum (Il)-resistant human leukemia HL-60 cells and down-regulated by cell differentiation. J Biol Chem 269:29085–29093.

    PubMed  Google Scholar 

  143. Oude Elferink RPJ, Jansen PLM (1994) The role of the canalicular multispecific organic anion transporter in the disposal of endo- and xenobiotics. Pharmacol Ther 64:77–97.

    Article  Google Scholar 

  144. Smit JJM, Schinkel AH, Oude Elferink RPJ, Groen AK, Wagenaar E, van Deemter L, Mol CAAM, Ottenhoff R, van der Lugt NMT, van Roon MA, van der Valk MA, Offerhaus GJA, Berns AJM, Borst P (1993) Homozygous disruption of the murine mdr2 P-glycoprotein gene leads to a complete absence of phospholipid from bile and to liver disease. Cell 75:451–462.

    Article  PubMed  CAS  Google Scholar 

  145. Schinkel AH, Smit JJM, van Tellingen O, Beijnen JH, Wagenaar E, van Deemter L, Mol CAAM, van der Valk MA, Robanus-Maandag EC, te Riele HPJ, Berns AJM, Borst P (1994) Disruption of the mouse mar1a P-glycoprotein gene leads to a deficiency in the blood-brain barrier and to increased sensitivity to drugs. Cell 77:491–502.

    Article  PubMed  CAS  Google Scholar 

  146. Reutz S, Gros P (1994) Phosphatidylcholine translocase: A physiological role for the mdr2 gene. Cell 77:1071–1081.

    Article  Google Scholar 

  147. Tsuruo T, Iida H, Tsukagoshi S, Sakurai Y (1981) Overcoming of vincristine resistance in P388 leukemia in vivo and in vitro through enhanced cytotoxicity of vincristine and vinblastine by verapamil. Cancer Res 41:1967–1972.

    PubMed  CAS  Google Scholar 

  148. Ford JM, Hait WN (1991) Pharmacology of drugs that alter multidrug resistance in cancer. Pharmacol Rev 42:155–199.

    Google Scholar 

  149. Ford JM, Hait WN (1993) Pharmacologic circumvention of multidrug resistance. Cytotechnology 12:171–212.

    Article  PubMed  CAS  Google Scholar 

  150. Raderer M, Scheithauer W (1993) Clinical trials of agents that reverse multidrug resistance. A literature review. Cancer 72:3553–3563.

    Article  PubMed  CAS  Google Scholar 

  151. Gottesman MM, Pastan I (1989) Clinical trials of agents that reverse multidrug-resistance. J Clin Oncol 7:409–411.

    PubMed  CAS  Google Scholar 

  152. Sikic BI (1993) Modulation of multidrug resistance: At the threshold. J Clin Oncol 11:1629–1635.

    PubMed  CAS  Google Scholar 

  153. Foxwell BMJ, Mackie A, Ling V, Ryffel B (1989) Identification of the multidrug resistance-related P-glycoprotein as a cyclosporine binding protein. Mol Pharmacol 36:543–546.

    PubMed  CAS  Google Scholar 

  154. Safa AR (1988) Photoaffinity labeling of the moltidrug-resistance-related P-glycoprotein with photoactive analogs of verapamil. Proc Natl Acad Sci USA 85:7187–7191.

    Article  PubMed  CAS  Google Scholar 

  155. Rao US, Scarborough GA (1994) Direct demonstration of high affinity interactions of immunosuppressant drugs with the drug binding site of the human P-glycoprotein. Mol Pharmacol 45:773–776.

    PubMed  CAS  Google Scholar 

  156. Cole SPC, Downes HF, Slovak ML (1989) Effect of calcium antagonists on the chemosensitivity of two multidrug resistant human tumour cell lines which do not overexpress P-glycoprotein. Br J Cancer 59:42–46.

    Article  PubMed  CAS  Google Scholar 

  157. Gekeler V, Boer R, Ise W, Sanders KH, Schachtele C, Beck J (1995) The specific bisindolylmaleimide PKC-inhibitor GF 109203X efficiently modulates MRP-associated multiple drug resistance. Biochem Biophys Res Commun 206:119–126.

    Article  PubMed  CAS  Google Scholar 

  158. Gekeler V, Ise W, Sanders KH, Ulrich W-R, Beck J (1995) The leukotriene LTD4 receptor antagonist MK571 specifically modulates MRP associated multidrug resistance. Biochem Biophys Res Commun 208:345–352.

    Article  PubMed  CAS  Google Scholar 

  159. van der Graaf WTA, de Vries EGE, Timmer-Bosscha H, Meersma GJ, Mesander G, Vellenga E, Mulder NH (1994) Effects of amiodarone, cyclosporin A, and PSC 833 on the cytotoxicity of mitroxantrone, doxorubicin, and vincristine in non-P-glycoprotein human small cell lung cancer cell lines. Cancer Res 54:5368–5373.

    PubMed  Google Scholar 

  160. Versantvoort CHM, Schuurhuis GJ, Pinedo HM, Eekman CA, Kuiper CM, Lankelma J, Broxterman H (1993) Genistein modulates the decreased drug accumulation in non-P-glycoprotein mediated multidrug resistant tumour cells. Br J Cancer 68:939–946.

    Article  PubMed  CAS  Google Scholar 

  161. Gollapudi S, Thadepalli F, Kim CH, Gupta S (1995) Difloxacin reverses multidrug resistance in HL-60/AR cells that overexpress the multidrug resistance-related protein (MRP) gene. Oncol Res 7:73–85.

    Google Scholar 

  162. Zwelling LA, Slovak ML, Hinds M, Chan D, Parker E, Mayes J, Sie KL, Meltzer PS, Trent JM (1990) HT1080/DR4: A P-glycoprotein-negative human fibrosarcoma cell line exhibiting resistance to topoisomerase II-reactive drugs despite the presence of a drug-sensitive topoisomerase II. J Natl Cancer Inst 82:1553–1561.

    Article  PubMed  CAS  Google Scholar 

  163. de Jong S, Zijlstra JG, Mulder NH, de Vries EGE (1991) Lack of cross-resistance to fostriecin in a human small-cell lung carcinoma cell line showing topoisomerase II-related drug resistance. Cancer Chemother Pharmacol 28:461–464.

    Article  PubMed  Google Scholar 

  164. Griffith OW, Meister A (1979) Potent and specific inhibition of glutathione synthesis by buthionine sulfoximine (S-n-butyl homocysteine sulfoximine). J Biol Chem 254:7558–7560.

    PubMed  CAS  Google Scholar 

  165. Versantvoort CHM, Broxterman HJ, Bagrij T, Scheper RJ, Twentyman PR (1995) Regulation by glutathione of drug transport in multidrug-resistant human lung tumour cell lines overexpressing multidrug resistance-associated protein. Br J Cancer 72:82–89.

    Article  PubMed  CAS  Google Scholar 

  166. Meijer C, Mulder NH, Timmer-Bosscha H, Peters WHM, de Vries EGE (1991) Combined in vitro modulation of adriamycin resistance. Int J Cancer 49:582–586.

    Article  PubMed  CAS  Google Scholar 

  167. Lutzky J, Astor MB, Taub RN, Baker MA, Bhalla K, Gervasoni JE Jr, Rosado M, Stewart V, Krishna S, Hindenburg AA (1989) Role of glutathione and dependent enzymes in anthracycline-resistant HL60/AR cells. Cancer Res 49:4120–4125.

    PubMed  CAS  Google Scholar 

  168. Brophy NA, Marie JP, Rojas VA, Warnke RA, McFall PJ, Smith SD, Sikic BI (1994) Mdr1 gene expression in childhood acute lymphoblastic leukemias and lymphomas: A critical evaluation by four techniques. Leukemia 8:327–335.

    PubMed  Google Scholar 

  169. Futscher BW, Abbaszadegan MR, Domann F, Dalton WS (1994) Analysis of MRP mRNA in mitoxantrone-selected, multidrug-resistant human tumor cells. Biochem Pharmacol 47:1601–1606.

    Article  PubMed  CAS  Google Scholar 

  170. Lazaruk LC, Campling BG, Baer KA, Lam Y-M, Cole SPC, Deeley RG, Gerlach JH (1995) Drug resistance and expression of MRP and MDR1 in small cell lung cancer cell lines (abstr). Proc Am Assoc Cancer Res 36:1953.

    Google Scholar 

  171. Burger H, Nooter K, Zaman GJR, Sonneveld P, van Wingerden KE, Oostrum RG, Stoter G (1994) Expression of the multidrug resistance-associated protein (MRP) in acute and chronic leukemias. Leukemia 8:990–997.

    PubMed  CAS  Google Scholar 

  172. Chan HSL, Haddad G, Hipfner DR, Deeley RG, Cole SPC (1995) Sensitive detection of the multidrug resistance protein (MRP) in malignant cells (abstr). Proc Am Assoc Cancer Res 36:1941.

    Google Scholar 

  173. Krishnamachary N, Ma L, Zheng L, Safa AR, Cnter MS (1994) Analysis of MRP gene expression and function in HL60 cells isolated for resistance to adriamycin. Oncol Res 6:119–127.

    PubMed  CAS  Google Scholar 

  174. Hipfner DR, Gauldie SD, Deeley RG, Cole SPC (1994) Detection of the M, 190,000 multidrug resistance protein, MRP, with monoclonal antibodies. Cancer Res 54:5788–5792.

    PubMed  CAS  Google Scholar 

  175. Lalande ME, Ling V, Miller RG (1981) Hoechst 33342 dye uptake as a probe of membrane permeability changes in mammalian cells. Proc Natl Acad Sci USA 78:363–367.

    Article  PubMed  CAS  Google Scholar 

  176. Neyfakh AA (1988) Use of fluroescent dyes as molecular probes for the study of multidrug resistance. Exp Cell Res 174:168–176.

    Article  PubMed  CAS  Google Scholar 

  177. de Jong S, Holtrop M, de Vries H, de Vries EGE, Mulder NH (1992) Increased sensitivity of an adriamycin-resistant human small cell lung carcinoma cell line to mitochondrial inhibitors. Biochem Biophys Res Commun 182:877–885.

    Article  PubMed  Google Scholar 

  178. Feller N, Kuiper CM, Lankelma J, Ruhdal JK, Scheper RJ, Pinedo HM, Broxterman HJ (1995) Functional detection of MDR1/P170 and MRP/P190 mediated multidrug resistance in tumor cells by flow cytometry. Br J Cancer 72:543–549.

    Article  PubMed  CAS  Google Scholar 

  179. Twentyman PR, Rhodes T, Rayner S (1994) A comparison of rhodamine 123 accumulation and efflux in cells with P-glycoprotein-mediated and MRP-associated multidrug resistance phenotypes. Eur J Cancer 30A: 1360–1369.

    Article  PubMed  CAS  Google Scholar 

  180. Nooter K, Sonneveld P, Oostrum R, Herweijer H, Hagenbeek T, Valerio D (1990) Overexpression of the mdr1 gene in blast cells from patients with acute myelocytic leukemia is associated with decreased anthracycline accumulation that can be restored by cyclosporin-A. Int J Cancer 45:263–268.

    Article  PubMed  CAS  Google Scholar 

  181. Ross DD, Wooten PJ, Tong Y, Cornblatt B, Levy C, Sridhara R, Lee EJ, Schiffer CA (1994) Synergistic reversal of multidrug-resistance phenotype in acute myeloid leukemia cells by cyclosporin A and cremophor EL. Blood 83:1337–1347.

    PubMed  CAS  Google Scholar 

  182. Schuurhuis GJ, Broxterman HJ, Cervantes A, van Heijningen THM, de Lange JHM, Baak JPA, Pinedo HM, Lankelma J (1989) Quantitative determination of factors contributing to doxorubicin resistance in multidrug-resistant cells. J Natl Cancer Inst 81:1887–1892.

    Article  PubMed  CAS  Google Scholar 

  183. Rutherford AV, Willingham MC (1993) Ultrastructural localization of daunomycin in multidrug-resistant cultured cells with modulation of the multidrug transporter. J Histochem Cytochem 41:1573–1577.

    Article  PubMed  CAS  Google Scholar 

  184. Hindenburg AA, Baker MA, Gleyzer E, Stewart VJ, Case N, Taub RN (1987) Effect of verapamil and other agents on the distribution of anthracyclines and on reversal of drug resistance. Cancer Res 47:1421–1425.

    PubMed  CAS  Google Scholar 

  185. Burger H, Nooter K, Sonneveld P, van Wingerden KE, Zaman GJR, Stoter G (1994) High expression of the multidrug resistance-associated protein (MRP) in chronic and prolymphocytic leukaemia. Br J Haematol 88:348–356.

    Article  PubMed  CAS  Google Scholar 

  186. Beck J, Niethammer D, Gekeler V (1994) High mdrl and mrp-, but low topoisomerase Ila-gene expression in B-cell chronic lymphoycytic leukaemias. Cancer Lett 86:135–142.

    Article  PubMed  CAS  Google Scholar 

  187. Hart SM, Ganeshaguru K, Hoffbrand AV, Prentice HG, Mehta AB (1994) Expression of the multidrug resistance-associated protein (MRP) in acute leukemia. Leukemia 8:2163–2168.

    PubMed  CAS  Google Scholar 

  188. Schuurhuis GJ, Broxterman HJ, Ossenkoppele GJ, Baak JPA, Eekman CA, Kuiper CM, Feller N, van Heijningen THM, Klumper E, Pieters R, Lankelma J, Pinedo HM (1995) Functional multidrug resistance phenotype associated with combined overexpression of Pgp/MDR1 and MRP together with 1-β-D-arabinofuranosylcytosine sensitivity may predict clinical response in acute myeloid leukemia. Clin Cancer Res 1:81–93.

    PubMed  CAS  Google Scholar 

  189. Beck J, Handgretinger R, Dopfer R, Klingebiel T, Niethammer D, Gekeler V (1995) Expression of mdrl, mrp, topoisomerase IIα/β, and cyclin A in primary or relapsed states of acute lymphoblastic leukaemias. Br J Haematol 89:356–363.

    Article  PubMed  CAS  Google Scholar 

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  1. Susan P. C. Cole Ph.D.
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  2. Roger G. Deeley Ph.D.
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Editors and Affiliations

  1. The Cancer Institute of New Jersey, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, 679 Hoes Lane, Room 242, Piscataway, NJ, 08854, USA

    William N. Hait M.D., Ph.D.

  2. Department of Medicine, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, 679 Hoes Lane, Room 242, Piscataway, NJ, 08854, USA

    William N. Hait M.D., Ph.D.

  3. Department of Pharmacology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, 679 Hoes Lane, Room 242, Piscataway, NJ, 08854, USA

    William N. Hait M.D., Ph.D.

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Cole, S.P.C., Deeley, R.G. (1996). Multidrug Resistance Associated with Overexpression of MRP. In: Hait, W.N. (eds) Drug Resistance. Cancer Treatment and Research, vol 87. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-1267-3_2

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