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Nucleoside Transport Into Cells

Role of Nucleoside Transporters SLC28 and SLC29 in Cancer Chemotherapy
  • Marçal Pastor-Anglada
  • F. Javier Casado
Part of the Cancer Drug Discovery and Development book series (CDD&D)

Abstract

Nucleosides are taken up into cells by either concentrative nucleoside transporter (CNT; SLC28 gene family) or equilibrative nucleoside transporter (ENT; SLC29 gene family) nucleoside transporters, which differ in their substrate selectivity and their energy requirements. Both nucleoside transporter families have also been involved in the transmembrane transport of nucleoside-derived compounds, many of them currently used in antiviral and antitumoral therapies; hence, there is necessity for good knowledge about the function of these transporters. Some key points in the pharmacological understanding of these transporters are addressed. There is a long list of nucleoside derivatives with clinical relevance that are known to be transported by one or several nucleoside transporters; however, until recently little was known about the structural determinants that allow the molecular recognition of the substrates by their transporters. This will be a key point in the development of rationally designed new drugs. Other aspects of nucleoside transporters are also relevant to their function as drug transporters. On the one hand, several polymorphisms have been described in CNT and ENT proteins that could affect their activity, although thorough functional analysis awaits. On the other hand, tissue distribution of these transporters is not homogeneous among tissues, and their expression can be tightly regulated, thus opening the possibility of over- or underexpression of a particular transporter in transformed cells, as has been reported in several cases. All these properties of nucleoside transporters determine their role in the bioavailability and cell sensitivity to anticancer drugs, and the first studies linking nucleoside transporter function to drug sensitivity and clinical outcome in cancer patients are now reported.

Key Words

Concentrative nucleoside transporter equilibrative nucleoside transporter nucleoside uptake passive diffusion. 

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References

  1. 1.
    Belt JA, Marina NM, Phelps D, Crawford CR. Nucleoside transport in normal and neoplastic cells. Adv Enzyme Regul 1993;33:235–252.PubMedCrossRefGoogle Scholar
  2. 2.
    Griffith DA, Jarvis SM. Nucleoside and nucleobase transport systems of mammalian cells. Biochim Biophys Acta 1996; 1286:153–181.PubMedGoogle Scholar
  3. 3.
    Huang QQ, Yao SY, Ritzel MW, Pateron AR, Cass CE, Young JD. Cloning and functional expression of a complementary DNA encoding a mammalian nucleoside transport protein. J Biol Chem 1994;269:17,757–17,760.PubMedGoogle Scholar
  4. 4.
    Che M, Ortiz DF, Arias IM. Primary structure and functional expression of a cDNA encoding the bile canalicular purine-specific Na+-nucleoside cotrans-porter. J Biol Chem 1995;270:13,596–13,599.PubMedCrossRefGoogle Scholar
  5. 5.
    Ritzel MW, Yao SY, Huang MY, Elliott JF, Cass CE, Young JD. Molecular cloning and functional expression of cDNAs encoding a human Na+-nucleoside cotransporter (hCNT1). Am J Physiol 1997;272:C707–C714.PubMedGoogle Scholar
  6. 6.
    Wang J, Su SF, Dresser MJ, Schaner ME, Washington CB, Giacomini KM. Na+-dependent purine nucleoside transporter from human kidney: cloning and functional characterization. Am J Physiol 1997;273:F1058–F1065.PubMedGoogle Scholar
  7. 7.
    Griffits M, Beaumont N, Yao SY, et al. Cloning of a human nucleoside transporter implicated in the cellular uptake of adenosine and chemotherpeutic drugs. Nat Med 1997;3:89–93.CrossRefGoogle Scholar
  8. 8.
    Griffits M, Yao SY, Adibi F, et al. Molecular cloning and characterization of a nitrobenzylthioinosine-insensitive (ei) equilibrative nucleoside transporter from human placenta. Biochem J 1997;328:739–743.Google Scholar
  9. 9.
    Crawford CR, Patel DH, Naeve C, Belt JA. Cloning of the human equilibrative, nitrobenzylmercaptopurine riboside (NBMPR)-insensitive nucleoside transporter ei by functional expression in a transport-deficient cell line. J Biol Chem 1998; 273:5288–5293.PubMedCrossRefGoogle Scholar
  10. 10.
    Ritzel MW, Ng AM, Yao SY, et al. Molecular identification and characterization of novel human and mouse concentrative Na+-nucleoside cotransporter proteins (hCNT3 and mCNT3) broadly selective for purine and pyrimidine nucleosides (system cib). J Biol Chem 2001;276:2914–2927.PubMedCrossRefGoogle Scholar
  11. 11.
    Baldwin SA, Beal PR, Yao SYM, King AE, Cass CE, Young JD. The equilibrative nucleoside transporter family, SLC29. Plugers Arch Eur J Physiol 2004; 447:735–743.CrossRefGoogle Scholar
  12. 12.
    Lostao MP, Mata JF, Larráyoz IM, Inzillo SM, Casado FJ, Pastor-Anglada M. Electrogenic uptake of nucleosides and nucleoside-derived drugs by the human nucleoside transporter 1 (hCNT1) expressed in Xenopus laevis oocytes. FEBS Lett 2000;481:137–140.PubMedCrossRefGoogle Scholar
  13. 13.
    Chandrasena G, Giltay R, Patil SD, Bakken A, Unadkat JD. Functional expression of human intestinal Na+-dependent and Na+-independent nucleoside transporters inXenopus laevis oocytes. Biochem Pharmacol 1997;53:1909–1918.PubMedCrossRefGoogle Scholar
  14. 14.
    Ritzel MW, Yao SY, Ng AM, Mackey JR, Cass CE, Young JD. Molecular cloning, functional expression and chromosomal localization of a cDNA encoding a human Na+/nucleoside cotransporter (hCNT2) selective for purine nucleosides and uridine. Mol Membr Biol 1998;15:203–211.PubMedGoogle Scholar
  15. 15.
    Larráyoz I, Casado FJ, Pastor-Anglada M, Lostao P. Electrophysiological characterization of the human Na+/nucleoside cotransporter 1 (hCNT1) and role of adenosine on hCNT1 function. J Biol Chem 2004;8999–9007.Google Scholar
  16. 16.
    Smith KM, Ng AM, Yao SY, et al. Electrophysiological characterization of a recombinant human nucleoside transporter (hCNT1) produced in Xenopus oocytes. J Physiol 2004;558:807–823.PubMedCrossRefGoogle Scholar
  17. 18.
    Damaraju VL, Damaraju S, Young JD, et al. Nucleoside anticancer drugs: the role of nucleoside transporters in resistance to cancer chemotherapy. Oncogene2003; 22:7524–7536.PubMedCrossRefGoogle Scholar
  18. 19.
    Pastor-Anglada M, Molina-Arcas M, Casado FJ, Bellosillo B, Colomer D, Gil J. Nucleoside transporters in chronic lymphocytic leukaemia. Leukemia 2004; 18:385–393.PubMedCrossRefGoogle Scholar
  19. 20.
    Kong W, Engel K, Wang J. Mammalian nucleoside transporters. Current Drug Metab 2004;5:63–84.CrossRefGoogle Scholar
  20. 21.
    Mackey JR, Yao SY, Smit KM, et al. Gemcitabine transport in Xenopus oocytes expressing recombinant plasma membrane mammalian nucleoside transporters. J Natl Cancer Inst 1999;91:1876–1881.PubMedCrossRefGoogle Scholar
  21. 22.
    Dresser MJ, Gerstin KM, Gray AT, Loo DD, Giacomini KM. Electrophysiological analysis of the substrate selectivity of a sodium-coupled nucleoside transporter (rCNT1) expressed in Xenopus laevis oocytes. Drub Metab Dispos 2000;28:1135–1140.Google Scholar
  22. 23.
    Mata JF, GarcÃ-a-Manteiga JM, Lostao MP, et al. Role of the human concentrative nucleoside transporter (hCNT1) in the cytotoxic action of 5ï-deoxy-5-fluorouridine, an active intermediate metabolite of capecitabine, a novel oral anticancer drug. Mol Pharmacol 2001;59:1542–1548.PubMedGoogle Scholar
  23. 24.
    Galmarini CM, Mackey JR, Dumontet C. Nucleoside analogues and nucleobases in cancer treatment. Lancet Oncol 2002;3:415–424.PubMedCrossRefGoogle Scholar
  24. 25.
    Gray JH, Owen RP, Giacomini KM. The concentrative nucleoside transporter family, SLC28. Pflugers Arch Eur J Physiol2004;447:728–734.CrossRefGoogle Scholar
  25. 26.
    Zhang J, Visser F, Vickers MF, et al. Uridine binding motifs of human concentrative nucleoside transporters 1 and 3 produced in Saccharomyces cerevisiae. Mol Pharmacol 2004;64:1512–1520.CrossRefGoogle Scholar
  26. 27.
    Vickers MF, Zhang J, Visser F, et al. Uridine recognition motifs of human equilibrative nucleoside transporters 1 and 2 produced in Saccharomyces cerevisiae. Nucleosides Nucleotides Nucleic Acids 2004;23:361–373.PubMedCrossRefGoogle Scholar
  27. 28.
    Chang C, Swaan PW, Ngo LY, Lum PY, Patil SD, Unadkat JD. Molecular requirements of the human nucleoside transporter hCNT1, hCNT2, and hENT1. Mol Pharmacol 2004;65:558–570.PubMedCrossRefGoogle Scholar
  28. 29.
    Cano-Soldado P, Larráyoz IM, Molina-Arcas M, et al. Interaction of nucleoside inhibitors of HIV reverse transcriptase (NRT) with the concentrative nucleoside transporter 1 (hCNT1). AntivirTher 2005;9:993–1002.Google Scholar
  29. 30.
    Leabman MK, Huang CC, DeYoung J, et al. Natural variation in human membrane transporter genes reveals evolutionary and functional constraints. Proc Natl Acad Sci USA 2003; 100:5896–5901.PubMedCrossRefGoogle Scholar
  30. 31.
    Osato DH, Huang CC, Kawamoto M, et al. Functional characterization in yeast of genetic variants in the equilibrative nucleoside transporter, ENT1. Pharmaco-genetics 2003;13:297–301.Google Scholar
  31. 32.
    Gray JH, Mangravite LM, Owen RP, et al. Functional and genetic diversity in the concentrative nucleoside transporter, CNT1, in human populations. Mol Pharmacol 2004;65:512–519.PubMedCrossRefGoogle Scholar
  32. 33.
    Lai Y, Lee EW, Ton CC, Vijay S, Zhang H, Unadkat JD. Conserved residues F316 and G476 in the concentrative nucleoside transporter 1 (hCNT1) impact guanosine sensitivity and membrane expression, respectively. Am J Physiol Cell Physiol 2005; 288:C39–C45.PubMedGoogle Scholar
  33. 34.
    Gutierrez MM, Giacomini KM. Substrate selectivity, potential sensitivity and stoichiometry of nucleoside transport in brush border membrane vesicles from human kidney. Biochim Biophys Acta 1993;1149:202–208.PubMedCrossRefGoogle Scholar
  34. 35.
    Ruiz-Montasell B, Felipe A, Casado FJ, Pastor-Anglada M. Uridine transport in basolateral plasma membrane vesicles from rat liver. J Membr Biol 1992; 128:227–233.PubMedGoogle Scholar
  35. 36.
    Mercader J, GÓmez-Angelats M, del Santo B, Casado FJ, Felipe A, Pastor-Anglada M. Nucleoside uptake in rat liver parenchymal cells. Biochem J1996; 317:835–842.PubMedGoogle Scholar
  36. 37.
    Felipe A, Valdés R, del Santo B, Lloberas J, Casado FJ, Pastor-Anglada M. Na-dependent nucleoside transport in liver. Two different isoforms from the same gene family are expressed in liver parenchymal cells. Biochem J 1998;330:997–1001.PubMedGoogle Scholar
  37. 38.
    Valdés R, Ortega MA, Casado FJ, et al. Nutritional regulation of nucleoside transporter expression in rat small intestine. Gastroenterology 2000;119:1623–1630.PubMedCrossRefGoogle Scholar
  38. 39.
    Soler C, Felipe A, Mata JF, Casado FJ, Celada A, Pastor-Anglada M. Regulation of nucleoside transport by lipopolysaccharide, phorbol esters, and tumor necrosis factor-α in human B-lymphocytes. J Biol Chem 1998;273:26,939–26,945.PubMedCrossRefGoogle Scholar
  39. 40.
    Soler C, Valdés R, GarcÃ-a-Manteiga J, et al. Lipopolysaccharide-induced apoptosis of macrophages determines the up-regulation of concentrative nucleoside transporters CNT1 and CNT2 through tumor necrosis factor α-dependent and-independent mechanisms. J Biol Chem 2001;276:30,043–30,049.PubMedCrossRefGoogle Scholar
  40. 41.
    Soler C, GarcÃ-a-Manteiga J, Valdes R, et al. Macrophages require different nucleoside transport systems for proliferation and activation. FASEB J 2001;15:1979–1988.PubMedCrossRefGoogle Scholar
  41. 42.
    Soler C, Felipe A, GarcÃ-a-Manteiga J, et al. Interferon-regulates nucleoside transport systems in macrophages through signal transduction and activator of transduction factor (STAT1)-dependent and-independent signaling pathways. Biochem J 2003;375:777–783.PubMedCrossRefGoogle Scholar
  42. 43.
    Aymerich I, Pastor-Anglada M, Casado FJ. Long-term endocrine regulation of nucleoside transporters in rat intestinal epithelial cells. J Gen Physiol 2004; 124:505–512.PubMedCrossRefGoogle Scholar
  43. 44.
    Choi DS, Cascini MG, Mailliard W, et al. The type I equilibrative nucleoside transporter regulates ethanol intoxication and preference. Nat Neurosci 2004;7:855–861.PubMedCrossRefGoogle Scholar
  44. 45.
    del Santo B, Valdés R, Mata J, Felipe A, Casado FJ, Pastor-Anglada M. Differential expression and regulation of nucleoside transport systems in rat liver parenchymal and hepatoma cells. Hepatology 1998;28:1504–1511.PubMedCrossRefGoogle Scholar
  45. 46.
    Pastor-Anglada M, Felipe A, Casado FJ, del Santo B, Mata JF, Valdés R. Nucleoside transporters and liver cell growth. Biochem Cell Biol 1998;76:771–777.PubMedCrossRefGoogle Scholar
  46. 47.
    Pastor-Anglada M, Casado FJ, Valdés R, Mata J, GarcÃ-a-Manteiga J, Molina M. Complex regulation of nucleoside transporter expression in epithelial and immune system cells. Mol Membr Biol 2001;18:81–85.PubMedCrossRefGoogle Scholar
  47. 48.
    Dragan Y, Valdes R, GÓmez-Angelats M, et al. Selective loss of nucleoside carrier expression in rat hepatocarcinomas. Hepatology 2000;32:239–246.PubMedCrossRefGoogle Scholar
  48. 49.
    Fernández-Veledo S, Valdés R, Wallenius V, Casado FJ, Pastor-Anglada M. Upregulation of the high affinity pyrimidine-preferring nucleoside transporer CNT1 by tumor necrosis factor alpha and interleukin-6 in rat liver parenchymal cells. J Hepatol 2004;41:538–544.PubMedCrossRefGoogle Scholar
  49. 50.
    Valdes R, Casado FJ, Pastor-Anglada M. Cell cycle-dependent regulation of CNT1, a concentrative nucleoside transporter involved in the uptake of cell cycle-dependent nucleoside-derived anticancer drugs. Biochem Biophys Res Commun 2002;296:575–579.PubMedCrossRefGoogle Scholar
  50. 51.
    Duflot S, Riera B, Fernández-Veledo S, et al. ATP-sensitive K+ channels regulate the concentrative adenosine transporter CNT2 following activation by A(1) adenosine receptors. Mol Cell Biol 2004;24:2710–2719.PubMedCrossRefGoogle Scholar
  51. 52.
    Lee CW, Sokoloski JA, Sartorelli AC, Handschumacher RE. Differentiation of HL60 cells by dimethylsulfoxide activates a Na(+)-dependent nucleoside transport system. In Vivo 1994;8:795–801.PubMedGoogle Scholar
  52. 53.
    Frank DA, Mahajan S, Ritz J. B lymphocytes from patients with chronic lymphocytid leukemia contain signal transducer and activator of transcription (STAT) 1 and STAT3 constitutively phosphorylated on serine residues. J Clin Invest 1997;100:3140–3148.PubMedGoogle Scholar
  53. 54.
    Greenberg N, Schumm DE, Webb TE. Uridine kinase activities and pyrimidine nucleoside phosphorylation in fluoropyrimidine sensitive and resistant cell lines of theNovikoff hepatoma. Biochem J 1977; 164:379–387.PubMedGoogle Scholar
  54. 55.
    Sobrero AF, Moir RD, Bertino JR, Handschumacher RE. Defective facilitated diffusion of nucleosides, a primary mechanism of resistance to 5-fluoro-2′-deoxyuridine in the HCT-8 human carcinoma line. Cancer Res 1985;45:3155–3160.PubMedGoogle Scholar
  55. 56.
    White JC, Rathmell JP, Capizzi RL. Membrane transport influences de rate of accumulation of cytosine arabinoside in human leukemia cells. J Clin Invest 1987;79:380–387.PubMedCrossRefGoogle Scholar
  56. 57.
    Mackey JR, Mani RS, Selner M, et al. Functional nucleoside transporters are required for gemcitabine influx and manifestation of toxicity in cancer cell lines. Cancer Res 1998;58:4349–4357.PubMedGoogle Scholar
  57. 58.
    Chan TC. Augmentation of 1-β-D-arabinofuranosylcytosine cytotoxicity in human tumor cells by inhibiting drug efflux. Cancer Res 1989;2656–2660.Google Scholar
  58. 59.
    Crawford CR, Ng CY, Noel LD, Belt JA. Nucleoside transport in L1210 murine leukemia cells. Evidence for three transporters. J Biol Chem 265:9732–9736.Google Scholar
  59. 60.
    Crawford CR, Ng CY, Belt JA. Isolation and characterization of an L1210 cell line retaining the sodium-dependent carrier cif as its sole nucleoside transport activity. J Biol Chem 1990;265:13,730–13,734.PubMedGoogle Scholar
  60. 61.
    Alessi-Severini S, Gati WP, Paterson AR. Intracellular pharmacokinetis of 2-chlorodeoxyadenosine in leukemia cells from patients with chronic lymphocytic leukemia. Leukemia 1995;9:1674–1679.PubMedGoogle Scholar
  61. 62.
    Wright AM, Gati WP, Paterson AR. Enhancement of retention and cytotoxicity of 2-chlorodeoxyadenosine in cultured human leukemic lymphoblasts by nitrobenzylthioinosine, an inhibitor of equilibrative nucleoside transport. Leukemia 2000; 14:52–60.PubMedCrossRefGoogle Scholar
  62. 63.
    Cass CE, King KM, Montano JT, Janowska-Wieczorek A. A comparison of the abilities of nitrobenzylthioinosine, dilazep, and dipyridamole to protect human hematopoietic cells from 7-deazaadenosine (tubercidin). Cancer Res 1992;52:5879–5886.PubMedGoogle Scholar
  63. 64.
    Campas C, Lopez JM, Santidrian AF, et al. Acadesina activates AMPK and induces apoptosis in B-cell chronic lymphocytic leukemia cells but not in T lymphocytes. Blood 2003; 101:3674–3680.PubMedCrossRefGoogle Scholar
  64. 65.
    Lang TT, Selner M, Young JD, Cass CE. Acquisition of human concentrative nucleoside transporter 2 (hCNT2) activity by gene transfer confers sensitivity to fluoropyrimidine nucleosides in drug-resistant leukemia cells. Mol Pharmacol 2001;60:1143–1152.PubMedGoogle Scholar
  65. 66.
    GarcÃ-a-Manteiga J, Molina-Arcas M, Casado FJ, Mazo A, Pastor-Anglada M. Nucleoside transporter profiles in human pancreatic cancer cells. Role of hCNT1 in 2′,2′-difluorodeoxycytidine (gemcitabine) induced cytotoxicity. Clin Cancer Res 2003;9:5000–5008.Google Scholar
  66. 67.
    Lu X, Gong S, Monks A, Zaharevitz D, Moscow JA. Correlation of nucleoside and nucleobase transporter gene expression with antimetabolite drug cytotoxicity. J Exp Ther Oncol 2002;2:200–212.PubMedCrossRefGoogle Scholar
  67. 68.
    Pressacco J, Wiley JS, Jamieson GP, Erlichman C, Hedley DW. Modulation of the equilibrative nucleoside transporter by inhibitors of DNA synthesis. Br J Cancer 1995;72:939–942.PubMedGoogle Scholar
  68. 69.
    Pressacco J, Mitrovski B, Erlichman C, Hedley DW. Effect of thymidylate synthase inhibition on thymidine kinase activity and nucleoside transporter expression. Cancer Res 1995;55:1505–1508.PubMedGoogle Scholar
  69. 70.
    Frank DA, Mahajan S, Ritz J. Fludarabine-induced immunosuppression is associated with inhibition of STAT1 signaling. Nat Med 1999;5:444–447.PubMedCrossRefGoogle Scholar
  70. 71.
    Huang M, Wang Y, Cogut SB, Mitchell BS, Graves LM. Inhibition of nucleoside transport by protein kinase inhibitors. J Pharmacol Exp Ther 2003;304:753–760.PubMedCrossRefGoogle Scholar
  71. 72.
    Gati WP, Paterson AR, Belch AR, et al. Es nucleoside transporter content of acute leukemia cells: role in cell sensitivity to cytarabine (araC). Leuk Lymphoma 1998;32:45–54.PubMedGoogle Scholar
  72. 73.
    Wright AM, Paterson AR, Sowa B, Akabutu JJ, Grundy PE, Gati WP. Cytotoxicity of 2-chlorodeoxyadenosine and arabinosylcytosine in leukaemic lymphoblasts from paediatric patients: significance of cellular nucleoside transporter content. Br J Haematol 166:528–537.Google Scholar
  73. 74.
    Stam RW, den Boer ML, Meijerink JP, et al. Differential mRNA expression of Ara-C-metabolizing enzymes explains Ara-C sensitivity in MLL gene-rearranged infant acute lymphoblastic leukemia. Blood 2003;101:1270–1276.PubMedCrossRefGoogle Scholar
  74. 75.
    Molina-Arcas M, Bellosillo B, Casado FJ, et al. Fludarabine uptake mechanisms in B-cell chronic lymphocytic leukemia. Blood 2003; 101:2328–2334.PubMedCrossRefGoogle Scholar
  75. 76.
    Mackey JR, Galmarini CM, Graham KA, et al. Quantitative analysis of nucleoside transporter and metabolism gene expression in chronic lymphocytic leukemia (CLL)-Identification of fludarabine-sensitive and insensitive populations. Blood 2005;105:767–774.PubMedCrossRefGoogle Scholar
  76. 77.
    Molina-Arcas M, Marcé S, Villamor N, et al. Equilibrative nucleoside transporter-2 (hENT2) protein correlates with ex vivo sensitivity to fludarabine in chronic lymphocytic leukemia (CLL)-cells. Leukemia 2005;19:64–68.PubMedGoogle Scholar
  77. 78.
    Galmarini CM, Thomas X, Calvo F, et al. In vivo mechanisms of resistance to cytarabine in acute myeloid leukemia. Br J Haematol 2002;117:860–868.PubMedCrossRefGoogle Scholar
  78. 79.
    Pennycooke M, Chaudary N, Shuralyova I, Zhang Y, Coe IR. Differential expres-sion of human nucleoside transporters in normal and tumor tissue. Biochem Biophys Res Commun 2001;280:951–959.PubMedCrossRefGoogle Scholar
  79. 80.
    Mackey JR, Jennings LL, Clarke ML, et al. Immunohistochemical variation of human equilibrative nucleoside transporter 1 protein in primary breast cancers. Clin Cancer Res 2002;8:110–116.PubMedGoogle Scholar
  80. 81.
    Dabbagh L, Coupland RW, Cass CE, Mackey JR. Immunohistochemical variation of human equilibrative nucleoside transporter 1 protein in primary breast cancers. Clin Cancer Res 2003;9:3213, 3214.PubMedGoogle Scholar
  81. 82.
    Reiman T, Clarke ML, Dabbagh L, et al. Differential expression of human equilibrative nucleoside transporter 1 (hENT1) protein in the Reed-Sternberg cells of Hodgkin′s disease. Leuk Lymphoma 2002; 1435–1440.Google Scholar
  82. 83.
    Farré X, Guillén-GÓmez E, Sánchez L, et al. Expression of the nucleoside-derived drug transporters hCNT1, hENT1 and hENT2 in gynecologic tumors. Int J Cancer 2004;112:959–966.PubMedCrossRefGoogle Scholar
  83. 84.
    Spratlin J, Sangha R, Glubrecht D, et al. The absence of human equilibrative nucleoside transporter 1 is associated with reduced survival in patients with gemcitabine-treated pancreas adenocarcinoma. Clin Cancer Res 2004; 10:6956–6961.PubMedCrossRefGoogle Scholar
  84. 85.
    Gloeckner-Hofmann K, Guillén-GÓmez E, Schmidtgen C, et al. Expression of the high-affinity fluoropyrimidine-preferring nucleoside tansporter (hCNT1) correlates with decreased disease-free survival in breast cancer. Submitted.Google Scholar

Copyright information

© Humana Press Inc., Totowa, NJ 2006

Authors and Affiliations

  • Marçal Pastor-Anglada
    • 1
  • F. Javier Casado
    • 2
  1. 1.University of BarcelonaBarcelonaSpain
  2. 2.Department of Biochemistry and Molecular BiologyUniversity of BarcelonaBarcelonaSpain

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