Abstract
Gene expression of dihydropyrimidine dehydrogenase (DPD) and newly multidrug resistance-associated protein (MRP) was found to correlate well with primary 5-FU resistance in 7 human gastrointestinal cancer cell lines. Although mRNA and protein levels of thymidylate synthase (TS) did not relate to the resistance, 5-FU treatment revealed a remarkable increase of TS expression. Such enhanced TS expression was more significant than DPD and MRP, and observed less in 5-FU sensitive cells. DPD and MRP expression levels can predict primary 5-FU resistance, and TS may be a potent predictor of cellular 5-FU resistance after 5-FU treatment.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ATP-Binding Cassette Transporters / metabolism*
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Antimetabolites, Antineoplastic / pharmacology*
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Biomarkers
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Dihydrouracil Dehydrogenase (NADP)
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Drug Resistance, Multiple
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Drug Resistance, Neoplasm
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Drug Screening Assays, Antitumor
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Fluorouracil / pharmacology*
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Gastrointestinal Neoplasms / drug therapy
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Gastrointestinal Neoplasms / enzymology*
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Gastrointestinal Neoplasms / metabolism
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Gene Expression Regulation, Neoplastic
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Humans
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Multidrug Resistance-Associated Proteins
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Oxidoreductases / metabolism*
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RNA, Messenger / metabolism
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Thymidylate Synthase / metabolism*
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Tumor Cells, Cultured
Substances
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ATP-Binding Cassette Transporters
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Antimetabolites, Antineoplastic
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Biomarkers
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Multidrug Resistance-Associated Proteins
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RNA, Messenger
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Oxidoreductases
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Dihydrouracil Dehydrogenase (NADP)
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Thymidylate Synthase
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Fluorouracil