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KMID : 0578320080260040344
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Molecules and Cells
2008 Volume.26 No. 4 p.344 ~ p.349
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Thymidylate Synthase and Dihydropyrimidine Dehydrogenase Levels Are Associated with Response to 5-Fluorouracil in Caenorhabditis elegans
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Kim Seong-Seop
Park Dae-Hun
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Abstract
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5-Fluorouracil (5-FU), a pyrimidine antagonist, has a long history in cancer treatment. The targeted pyrimidine biosynthesis pathway includes dihydropyrimidine dehydrogenase (DPD), which converts 5-FU to an inactive metabolite, and thymidylate synthase (TS), which is a major target of 5-FU. Using Caenorhabditis elegans as a model system to study the functional and resistance mechanisms of anti-cancer drugs, we examined these two genes in order to determine the extent of molecular conservation between C. elegans and humans. Overexpression of the worm DPD and TS homologs (DPYD-1 and Y110A7A.4, respectively) suppressed germ cell death following 5-FU exposure. In addition, DPYD-1 depletion by RNAi resulted in 5-FU sensitivity, while treatment with Y110A7A.4 RNAi and 5-FU resulted in similar patterns of embryonic death. Thus, the pathway of 5-FU function appears to be highly conserved between C. elegans and humans at the molecular level.
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KEYWORD
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5-fluorouracil, `K=EaEO~ae, dihydropyrimidine dehydrogenase, thymidylate synthase
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