Dihydropyrimidine dehydrogenase, multidrug resistance-associated protein, and thymidylate synthase gene expression levels can predict 5-fluorouracil resistance in human gastrointestinal cancer cells

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.