Elevated expression of thymidylate synthase cycle genes in cisplatin-resistant human ovarian carcinoma A2780 cells.
- 1 February 1988
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 85 (3), 650-653
- https://doi.org/10.1073/pnas.85.3.650
Abstract
Activity of the thymidylate synthase cycle was compared in the human ovarian carcinoma cell line A2780 and a subline that is resistant to cisplatin by a factor of 3. Resistant cells exhibited a 3-fold increase in mRNA for both dihydrofolate reductase (5,6,7,8-tetrahydrofolate:NADP+-oxidoreductase, EC 1.5.1.3) and thymidylate synthase (5,10-methylenetetrahydrofolate:dUMP C-methyltransferase, EC 2.1.1.45) when compared with the parent line. Resistance to cisplatin also resulted in a 2.5-fold increase in enzyme activity for dihydrofolate reductase and thymidylate synthase; however, this increase did not result from amplification of the genes for these two enzymes. These data suggest that the initial step of cisplatin resistance in A2780 cells is a consequence of enhanced expression of the thymidylate synthase cycle.This publication has 19 references indexed in Scilit:
- Inhibition of methionine uptake by methotrexate in mouse leukemia L1210 cellsCancer Chemotherapy and Pharmacology, 1987
- Biochemical basis for cisplatin and 5-fluorouracil synergism in human ovarian carcinoma cells.Proceedings of the National Academy of Sciences, 1986
- ALKYLATING-AGENTS - INVITRO STUDIES OF CROSS-RESISTANCE PATTERNS IN HUMAN CELL-LINES1986
- Cell-cycle-directed regulation of thymidylate synthase messenger RNA in human diploid fibroblasts stimulated to proliferateJournal of Molecular Biology, 1986
- Establishment of cross-resistance profiles for new agents.1983
- Isolation of a cDNA clone for human X-linked 3-phosphoglycerate kinase by use of a mixture of synthetic oligodeoxyribonucleotides as a detection probe.Proceedings of the National Academy of Sciences, 1983
- Multiple forms of human dihydrofolate reductase messenger RNAJournal of Molecular Biology, 1982
- A rapid radiometric assay for dihydrofolate reductaseAnalytical Biochemistry, 1978
- The regulation of folate and methionine metabolismBiochemical Journal, 1976
- A rapid, radiochemical-ligand binding assay for methotrexateAnalytical Biochemistry, 1976