Severe folate restriction results in depletion of and alteration in the composition of the intracellular folate pool, moderate sensitization to methotrexate and trimetrexate, upregulation of endogenous DHFR activity, and overexpression of metallothionein II and folate receptor alpha that, upon folate repletion, confer drug resistance to CHL cells

Journal of Experimental Therapeutics and Oncology

Volumn 2, Issue 5, 2002, Pages 264-277

  Zhu, Wei Yong ^a   Bunni, M ^c   Priest, D G ^c   DiCapua, J L ^a   Dressler, J M ^a   Chen, Z ^a   Melera, Peter W ^a,b  

^a UNIVERSITY OF MARYLAND SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF MARYLAND   (United States)

^c MEDICAL UNIVERSITY OF SOUTH CAROLINA   (United States)

Author keywords

Antifolate resistance; DHFR; Folate depletion; Folate receptor; Metallothionein; Translation

Indexed keywords

CELL RECEPTOR; DIHYDROFOLATE REDUCTASE; FOLATE RECEPTOR ALPHA; FOLIC ACID; METALLOTHIONEIN; METHOTREXATE; TRIMETREXATE; UNCLASSIFIED DRUG;

ANIMAL CELL; ARTICLE; CELL CULTURE; CELL GROWTH; CONTROLLED STUDY; DRUG MECHANISM; DRUG RESISTANCE; DRUG SENSITIVITY; GENE ACTIVITY; GENE CONTROL; GENE OVEREXPRESSION; GENETIC TRANSCRIPTION; GENETIC TRANSFECTION; NONHUMAN; PRIORITY JOURNAL; STEADY STATE; TRANSCRIPTION REGULATION;

ANIMALS; CARRIER PROTEINS; CELLS, CULTURED; CRICETINAE; CRICETULUS; DRUG RESISTANCE; FOLIC ACID; FOLIC ACID ANTAGONISTS; LEUCOVORIN; METALLOTHIONEIN; METHOTREXATE; RECEPTORS, CELL SURFACE; TETRAHYDROFOLATE DEHYDROGENASE; TRIMETREXATE; UP-REGULATION;

EID: 0036733677     PISSN: 13594117     EISSN: None     Source Type: Journal    
DOI: 10.1046/j.1359-4117.2002.01049.x     Document Type: Article

References (60)

1. Folate cycle kinetics in human breast cancer cells
2. Drug resistance: Inhibitors of folate metabolism
3. The turnover of folate coenzymes in murine lymphoma cells
4. Long term remission in childhood acute leukemia: Use of infrequent infusions of methotrexate: Supportive role of platelet transfusions and citrovorum factor
5. Head and neck cancer: III. Toxicity of 24 hour infusions of methotrexate and protection by leucovorin in patients with epidermoid carcinomas
6. In vitro folate deficiency induces deoxynucleotide pool imbalance, apoptosis, and mutagenesis in Chinese hamster ovary cells
7. Folate deficiency causes uracil misincorporation into human DNA and chromosome breakage: Implications for cancer and neuronal damage
8. Folate deficiency in rats induces DNA strand breaks and hypomethylation within the p 53 tumor suppressor gene
9. The effects on 4-aminoantifolates on 5-formyltetrahydrofolate metabolism in L1210 cells
10. Folate-pool interconversions and inhibition of biosynthetic processes after exposure of L1210 leukemia cells to antifolates. Experimental and network thermodynamic analyses of the role of dihydrofolate polyglutamates in antifolate action in cells
11. Tumor resistance to antimetabolites
12. Membrane transport of natural folates and antifolate compounds in murine L1210 leukemia cells: Role of carrier- and receptor-mediated transport systems
13. Distinguishing between receptor-α-mediated transport and reduced folate carrier-mediated transport in L1210 leukemia cells
14. Folate receptors
15. The rate of folate receptor alpha (FRα) synthesis in folate depleted CHL cells is regulated by a translational mechanism sensitive to media folate levels, while stable overexpression of its mRNA is mediated by gene amplification and an increase in transcript half life
16. Metallothionein is overexpressed by hamster fibroblasts selected for growth in 15 pM folinic acid and provides a growth advantage in low folate
17. Overexpression of metallothionein confers resistance to anticancer drugs
18. Metallothionein null cells have increased sensitivity to anticancer drugs
19. Identification of a membrane-associated folate-binding protein in human leukemic CCRFCEM cells with transport-related methotrexate resistance
20. Functional aspects of membrane folate receptors in human breast cancer cells with transport-related resistance to methotrexate
21. Contemporary issues in toxicology. Role of metallothionein in carcinogenesis
22. Effects of folate receptor expression following stable transfection into wild type and methotrexate transport-deficient ZR-75-1 human breast cancer cells
23. Stable transfectants of human MCF-7 breast cancer cells with increased levels of the human folate receptor exhibit an increased sensitivity to antifolates
24. Tissue folate polyglutamate chain length determination by electrophoresis as thymidylate synthase-fluorodeoxyuridylate ternary complexes
25. A filter assay for thymidylate synthase using 5-fluoro-2′-deoxyuridylate as an active site titrant
26. Role of methylenetetrahydrofolate depletion in methotrexate-mediated intracellular thymidylate synthesis inhibition in cultured L1210 cells
27. Disposition of leucovorin and its metabolites in dietary folic acid-depleted mice: Comparison between tumor, liver, and plasma
28. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding
29. Expression of a folate binding protein in L1210 cells grown in low folate medium
30. Methotrexate transport in variant human CCRF-CEM leukemia cells with elevated levels of the reduced folate carrier. Selective effect on carrier-mediated transport of physiological concentrations of reduced folates
31. Two different species of dihydrofolate reductase in mammalian cells differentially resistant to Amethopterin and Methasquin
32. Allelic variation in the dihydrofolate reductase gene at amino acid position 95 contributes to antifolate resistance in Chinese hamster cells
33. Increased expression and characterization of two distinct folate binding proteins in murine erythroleukemia cells
34. Differential sterospecificities and affinities of folate receptor isoforms for folate compounds and antifolates
35. Selective amplification of polymorphic dihydrofolate reductase gene loci in Chinese hamster cells
36. Inhibition of thymidylate synthase by poly-γ-glutamyl derivatives of folate and methotrexate
37. Inhibition of AICAR transformylase by methotrexate and dihydrofolic acid polyglutamates
38. Basal levels of metallothionein I and II in mouse embryo fibroblasts enhance growth in low folate through a cell cycle mediated pathway
39. Expression of a folate binding protein in L1210 cells grown in low folate medium
40. Transfection of a glycosylated phosphatidylinositol-anchored folate binding protein complementary DNA provides cells with the ability to survive in low folate medium
41. Folate receptor allows cells to grow in low concentrations of 5-methyl tetrahydrofolate
42. Downstream molecular determinants of response to 5-fluorouracil and antifolate thymidylate synthase inhibitors
43. Folate depletion increases sensitivity of solid tumor cell lines to 5-fluorouracil and antifolates
44. In vitro activity of novel antifolates against human squamous carcinoma cell lines of the head and neck with inherent resistance to methotrexate
45. Resistance to classical and nonclassical antifolates results from selection of CHL cells for growth in low folate
46. Multiple mechanisms of resistance to polyglutamatable and lipophilic antifolates in mammalian cells: Role of increased folylpolyglutamylation, expanded folate pools, and intralysosomal drug sequestration
47. Evidence for a localized conversion of endogenous tetrahydrofolate cofactors to dihydrofolate as an important element in antifolate action in murine leukemia cells
48. Compartmentation of intracellular folates. Failure to interconvert tetrahydrofolate cofactors to dihydrofolate in mitochondria of L1210 leukemia cells treated with trimetrexate
49. Autoregulation of human thymidine synthase messenger RNA translation by thymidylate synthase
50. Specific binding of human dihydrofolate reductase protein to dihydrofolate reductase messenger RNA in vitro
51. Dihydrofolate reductase protein inhibits its own translation by binding to dihydrofolate reductase mRNA sequences within the coding region
52. Folate deficiency-induced oxidative stress and apoptosis are mediated via homocysteine-dependent overproduction of hydrogen peroxide and enhanced activation of NF-kappaB in human Hep G2 cells
53. Thymidylate synthase protein and p53 mRNA form an in vivo ribonucleoprotein complex
54. Dihydrofolate influences the activity of Escherichia coli dihydrofolate reductase synthesized de novo
55. Antifolate-resistant Chinese hamster cells. MRNA directed overproduction of multiple dihydrofolate reductases from a series of independently derived sublines containing amplified dihydrofolate reductase genes
56. Heat shock proteins
57. The 90-kDa heat shock protein, HSP90, binds and protects casein kinase II from self-aggregation and enhances its kinase activity
58. Isomerase and chaperone activity of prolyl isomerase in the folding of carbonic anhydrase
59. Cyclophilin-promoted folding of mouse dihydrofolate reductase does not include the slow conversion of the late-folding intermediate to the active enzyme