211
Views
46
CrossRef citations to date
0
Altmetric
Original Article

Methotrexate Transport and Resistance

Pages 215-224 | Received 30 Oct 1997, Published online: 01 Jul 2009

References

  • Fisher G.A. Defective transport of amethopterin (methotrexate) as a mechanism of resistance to the antimetabolite in L5178Y leukemic cells. Biochem Pharmacol. 1960; 11: 1233–1234
  • Goldman I.D., Lichtenstein N.S., Oliverio V.T. Carrier-mediated transport of the folic acid analogue, methotrexate, in LI210 leukemia. J Biol Chem 1968; 243: 5007–5017
  • Sirotnak F.M., Kurita F.M., Hutchison D.J. On the nature of a transport alteration detemining resistance to amethopterin in the LI210 leukemia. Cancer Res 1968; 28: 75–80
  • Henderson G.B., Zevely E.M. Transport of methotrexate in LI210 cells: effect of ions on the rate and extent of uptake. Arch Biochem Biophys 1980; 200: 149–55
  • Henderson G.B., Zevely E.M. Transport routes utilized by LI210 cells for the influx and efflux of methotrexate. J Biol Chem 1984; 259: 1526–1531
  • Henderson G.B., Zevely E.M. Characterization of the multiple transport routes for methotrexate in LI210 cells using phthalate as a model anion substrate. J Membr Biol 1985; 85: 263–8
  • Flintoff W.F., Essani K. Methotrexate-resistant Chinese hamster ovary cells contain a dihydrofolate reductase with an altered affinity for methotrexate. Biochemistry 1980; 18: 4321–1327
  • Flintoff W.F., Davidson S.V., Siminovitch L. Isolation and partial characterization of three methotrexate-resistant phenotypes from Chinese hamster ovary cells. Somatic Cell Genet 1976; 2: 245–261
  • Ohnuma T., Lo R.J., Scanlon K.J., Kamen B.A., Ohnoshi T., Wolman S.R., Holland J.F. Evolution of methotrexate resistance of human acute lymphoblastic leukemia cells in vitro. Cancer Res 1985; 45: 1815–1822
  • Cowan K.H., Jolivet J. A methotrexate-resistant human breast cancer cell line with multiple defects, including diminished formation of methotrexate polyglutamates. J Biol Chem 1984; 259: 10793–10800
  • Dixon K.H., Trepel J.B., Eng S.C., Cowan K.H. Folate transport and the modulation of antifolate sensitivity in a methotrexate-resistant human breast cancer cell line. Cancer Communications 1991; 3: 357–365
  • Schuetz J.D., Westin E.H., Matherly L.H., Pincus R., Swerdlow P.S., Goldman I.D. Membrane protein changes in an LI210 leukemia cell line with a translocation defect in the methotrexate-tetrahydrofolate cofactor transport carrier. J Biol Chem. 1989; 264: 16261–16261
  • Sirotnak F.M., Moccio D.M., Kellehcr L.E., Goutas L.J. Relative frequency and kinetic properties of transport-defective phenotypes among methotrexate-resistant LI210 clonal cell lines derived in vivo. Cancer Res 1981; 41: 4447–4452
  • Dixon K.H., Lanpher B.C., Chiu J., Kelley K., Cowan K.H. A novel cDNA restores reduced folate carrier activity and methotrexate sensitivity to transport deficient cells. J Biol Chem 1994; 269: 17–20
  • Williams F.R.M., Maurray R.C., Underhill T.M., Flintoff W.F. Isolation of a hamster cDNA clone coding for a function involved in methotrexate uptake. J Biol Chem 1994; 269: 5810–5816
  • Prasad P.D., Ramamoorthy S., Leibach F.H., Ganapathy V. Molecular cloning of the human placental folate transporter. Biochem Biophys Res Commun 1995; 206: 681–687
  • Williams F.M., Flintoff W.F. Isolation of a human cDNA that complements a mutant hamster cell defective in methotrexate uptake. J Biol Chem 1995; 270: 2987–2992
  • Wong S.C., Proefke S. A. A. B., Matherly L.H. Isolation of human cDNAs that restore methotrexate sensitivity and reduced folate carrier activity in methotrexate transport-deficient Chinese hamster ovary cells. J Biol Chem 1995; 270: 17468–17475
  • Moscow J.A., Gong M., He R., Sgagias M.K., Dixon K.H., Anzick S.L., Meltzer P.S., Cowan K.H. Isolation of a gene encoding a human reduced folate carrier(RFC1)and analysis of its expression in transport-deficient, methotrexate-resistant human breast cancer cells. Cancer Res 1995; 55: 3790–3794
  • Brigle K.E., Spinella M.J., Sierra E.E., Goldman I.D. Characterization of a mutation in the reduced folate carrier in a transport defective LI210 murine leukemia cell line. J Biol Chem 1995; 270: 22974–22979
  • Gong M.K., Yess J., Connolly T., Ivy S.P., Ohnuma T., Cowan K.H., Moscow J.A. Molecular mechanism of antifolate transport-deficiency in a methotrexate-resistant MOLT-3 cell line. Blood 1997; 89: 2494–2499
  • Moscow J.A., Connolly T., Myers T., Paull K., Cheng C.C., Cowan K.H. Reduced folate carrier gene expression in transfected and non-selected cell lines. Int J Cancer 1997; 72: 184–190
  • Alvarez M., Paull K., Monks A., Hose C., Lee J.-S., Weinstein J., Grever M., Bates S., Fojo T. Generation of a drug resistance profile by quantitation of mdr1 P-glycoprotein in the cell lines of the National Cancer Institute anticancer drug screen. J Clin Invest 1995; 95: 2205–2214
  • Gorlick R., Goker E., Trippet T., Stcinherz P., Elisseyeff Y., Mazumdar M., Flintoff W.F., Bertino J.R. Defective transport is a common mechanism of acquired methotrexate resistance in acute lymphocytic leukemia and is associated with decreased reduced folate carrier expression. Blood 1997; 89: 1013–1018
  • Murray R.C., Williams F.M.R., Flintoff W.F. Structural organization of the reduced folate carrier gene in Chinese hamster ovary cells. J Biol Chem 1996; 271: 19174–19179
  • Tolner B., Roy K., Sirotnak F. Organization, structure and alternative splicing of the murine RFC-1 gene encoding a folate transporter. Gene 1997; 189: 1–7
  • Gong M., Cowan K.H., Moscow J.A. Analysis of transcription of multiple 5′ untranslated regions of the human Reduced Folate Carrier (RFC1) gene. Proc Am Assn Cancer Res 1997; 38: 1082
  • Zhang L., Wong S.C., Matherly L.H. Upstream gene organization and transcript heterogeneity of he human reduced folate carrier. Proc Am Assn Cancer Res 1997; 38: 1084A
  • Evans W.E., Crom W.R., Stewart C.F., Bowman W.P., Chen C.-H., Abromovitch M., Simone J.V. Methotrexate systemic clearance influences the probability of relapse in children with standard-risk acute lymphocytic leukaemia. Lancet 1984; 1: 359
  • Evans W.E., Crom W.R., Abromovich M., Dodge R., Look A.T., Bowman W.P., George S.L., Pui C.-H. Clinical pharmacodynamics of high-dose methotrexate in acute lymphocytic leukemia -identification between concentration and effect. New England J Med 1986; 314: 471–475
  • Camitta B., Mahoney D., Leventhal B., Lauer S.J., Shuster J.J., Adair S., Civin C., Munoz L., Steuber P., Strother D., Kamen B.A. Intensive intravenous methotrexate and mercaptopurinc treatment of high-risk non-T, non-B acute lymphoblastic leukemia-, a Pediatric Oncology Group study. J Clin Oncol 1994; 12: 1383–1390
  • Seidel H., Nygaard R., Moe P.J., Jacobsen G., Lindqvist B., Slordal L. On the prognostic value of systemic methoptrexate clearance in childhood acute lymphocytic leukemia. Leukemia Res 1997; 21: 429–434
  • Henderson G.B. Folate-binding proteins. Annu Rev Nutr. 1990; 10: 319–35
  • Elwood P.C. Molecular cloning and characterization of the human folate-binding protein cDNA from placenta and malignant tissue culture. J Biol Chem 1989; 264: 14893–14901
  • Lacey S.W., Sanders J.M., Rothberg K.G., Anderson R.G.W., Kamen B.A. Complementary DNA for the folate binding protein correctly predicts anchoring to the membrane by glycosyl-phosphatidylinositol. J Clin Invest 1989; 84: 715–720
  • Ratnam M., Marquardt H., Duhring J.L., Freisheim J.H. Homologous membrane folate binding proteins in human placenta: cloning and sequence of a cDNA. Biochemistry 1989; 28: 8249–8254
  • Sadasivan E., Rothenberg S.P. The complete amino acid sequence of a human folate binding protein from KB cells determined from the cDNA. J Biol Chem 1989; 264: 5806–5811
  • Jansen G., Westerhof G.R., Kathmann I., Rademaker B.C., Rijksen G., Schornagel J.H. Identification of a membrane-associated folate-binding protein in human leukemic CCRF-CEM cells with transport-related methotrexate resistance. Cancer Res 1989; 49: 2455–9
  • Chung K.N., Saikawa Y., Paik T.H., Dixon K.H., Mulligan T., Cowan K.H., Elwood P.C. Stable transfectants of human MCF-7 breast cancer cells with increased levels of human folate receptor exhibit increased sensitivity to antifolates. J Clin Invest 1993; 91: 1289–1294
  • Pinard M.-F., Jolivct J., Ratnam M., Kathmann I., Molthoff C, Westerhof R., Schornagel J.H., Jansen G. Functional aspects of membrane folate reeptors in human breast cancer cells with transport-related resistance to methotrexate. Cancer Chemother Pharmacol 1996; 38: 281–281
  • Dixon K., Mulligan T., Chung K., Elwood P., Cowan K. Effects of folate receptor expression following stable transfection into wild type and methotrexate transport-deficient ZR-75-1 human breast cancer cells. J Biol Chem 1992; 267: 24140–24147
  • Mauritz R.M., Kathmann I., Peters G.J., Pinedo H.M., Schornagel J.H., Priest D.G., Bunni M., Drori S., Assaraf Y.G., Jansen G. Characterization of a human CEM leukemia cell line with altered RFC-mediated transport of folic acid, reduced folates and tetrahydrofolate-based antifolates. Proc Am Assn Cancer Res 1997; 38: 654A
  • Tse A., Brigle K., Moran R. Dominant mutations in the reduced folate carrier confer resistance to 5, 10-dideaza-tetrahydrofolate (DDATHF) by causing efficient transport of folic acid. Proc Am Assn Cancer Res 1997; 38: 1085A
  • Henderson G.B., Strauss B.P. Characteristics of a novel transport system for folate compounds in wild-type and methotrexate-resistant LI210 cells. Cancer Res 1990; 50: 1709–14
  • Sierra E.E., Brigle K.E., Spinella M.J., Goldman I.D. pH dependence of methotrexate transport by the reduced folate carrier and the folate receptor in LI210 leukemia cells. Further evidence for a third route mediated at a low pH. Biochem Pharmacol 1997; 53: 223–231
  • Home D.W. Transport of folates and antifolates in liver. Proc Soc Exp Biol Medicine 1993; 202: 385–391
  • Galivan J. 5-Methyltetrahydrofolate transport by hepatoma cells and methotrexate-resistant sublines in culture. Cancer Res 1981; 41: 1757–62
  • Sclhub J., Rosenberg I.H. Folate transport in isolated brush border membrane vesicles from rat intestine. J Biol Chem 1981; 256: 4489–93
  • Said H.M., Ghishan F.K., Redha R. Folate transport by human intestinal brush-border membrane vesicles. Am J Physiol. 1987
  • Schron C.M., Washington C.J., Blitzer B.L. The transmembrane pH gradient drives uphill folate transport in rabbit jejunum. Direct evidence for folate/hydroxyl exchange in brush border membrane vesicles. J Clin Invest 1985; 76: 2030–3
  • Mason J.B., Shoda R., Haskell M., Selhub J., Rosenberg I.H. Carrier affinity as a mechanism for the pH-depcndence of folate transport in the small intestine. Biochim Biophys Acta 1990; 1024: 331–5
  • Kumar C., Mover M., Dudeja P., Said H. A protein-tyrosine kinase-regulated, pH-dependent carrier-mediated uptake system for folate in human colonic epithelial cell line NCM460. J Biol Chem 1997; 272: 6226–6231
  • Chiao J., Roy K., Tolner B., Yang C.-H., Sirotnak F.M. RFC-1 gene expression regulates folate absorption in mouse small intestine. J Biol Chem 1997; 272: 11165–11170
  • Wong S.C., McQuade R., Proefke S.A., Bhushan A., Matherly L.H. Human K562 transfectants expressing high levels of reduced folate carrier but exhibiting low transport activity. Biochem Pharmacol 1997; 53: 199–206
  • Saito H., Masuda S., Inui K.-i. Cloning and functional characterization of a novel rat organic anion transporter mediating basolateral uptake of methotrexate in the kidney. J Biol Chem 1996; 271: 20719–20725
  • Deutsch J.C., Kolhouse J.F. Folate and methotrexate interactions in the rat kidney. Cancer Res 1989; 49: 5858–5862
  • Kullak-Ublick G.A., Hagenbuch B., Stieger B., Schteingart C.D., Hofmann A.F., Wolkoff A.W., Meier P.J. Molecular and functional characterization of an organic anion transporting polypeptide cloned from human liver. Gastroenterology 1995; 109: 1274–1282
  • Masuda M., I'izuka Y., Yamazaki M., Nishigaki R., Kato Y., Ni'inuma K., Suzuki H., Sugiyama Y. Methotrexate is excreted into the bile by canalicular Multispecific Organic Anion Transporter in rats. Cancer Res 1997; 57: 3506–3510
  • Moscow J.A., Schneider E.S., Ivy S.P., Cowan K.H. Multidrug resistance. Cancer chemotherapy and biological response modifiers, H.M. Pinedo, D.L. Longo, B.A. Chabner. Elsevier, New York 1997, Annual 17
  • Leier I., Jedlitschky G., Buchholz U., Keppler D. Characterization of the ATP-dependent leukotricne C4 export carrier in mastozytoma cells. Eur J Biochem 1994; 220: 599–606
  • Leier I., Jedlitschky G., Buchholz U., Cole S.P.C., Deeley R.G., Keppler D. The MRP gene encodes an ATP-dependent export pump for leukotriene C4 and structurally related conjugates. J Biol Chem 1994; 269: 27807–27810
  • Loe D.W., Almquist K.C., Deeley R.G., Cole S.P.C. Multidrug resistance protein (MRP)-mediated transport of leukotriene C4 and chemotherapeutic agents in membrane vesicles. J Biol Chem 1996; 271: 9675–9682
  • Jedlitschky G., Leier I., Buchholz U., Center M., Keppler D. ATP-dependent transport of glutathione 5-conjugates by the multidrug resistance-associated protein. Cancer Res 1994; 54: 4833–4836
  • Leszczy:nska B.A., Pfaff E. Effect of depletion of cellular glutathione on methotrexate influx, efflux and retention in hepatocytes. Biochem Pharmacol 1985; 34: 1627–34
  • Kool M., de Haas M., Schefer G.L., Scheper R.J., van Eijk M.J.T., Juijn J.A., Baas F., Borst P. Analysis of expression of cMOAT (MRP2), MRP3, MRP4, and MRP5, homologues of the Multidrug Resistance-associated Protein gene (MRP1), in human cancer cell lines. Cancer Res 1997; 57: 3537–3547
  • Zhao R., Seither R., Brigle K.E., Sharina I.G., Wang P.J., Goldman I.D. Impact of overexpression of the reduced folate carrier (RFC1), an anion exchanger, on concentrative transport in murine LI210 leukemia cells. J Biol Chem 1997; 272: 21207–21212
  • Sirotnak F.M., Moccio D.M., Yang C.H. A novel class of genetic variants of the LI210 celll up-regulated for folate analogue transport inward. Isolation, characterization, and degree of metabolic instability of the system. J Biol Chem 1984; 259: 13139–13144
  • Matherly L.H., Czajkowski C.A., Angeles S.M. Identification of a highly glycosylated methotrexate membrane carrier in K562 human erythroleukemia cells up-regulated for tetrahydrofolate cofactor and methotrexate transport. Cancer Res 1991; 51: 3420–6
  • Jansen G., Westerhof G.R., Jarmasewski M.J.A., Kathmann I., Rijksen G., Schornagel G. Methotrexate transport in variant human CCRF-CEM leukemia cells with elevated levels of the reduced folate carrier. J Biol Chem 1990; 265: 18272–18277

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.