Thymidylate synthase and dihydropyrimidine dehydrogenase mRNA expression after administration of 5-fluorouracil to patients with colorectal cancer

Robert Mauritz, Cees J. Van Groeningen, Kees Smid, Gerrit Jansen, Herbert M. Pinedo, Godefridus J. Peters

Research output: Contribution to journalArticle

Abstract

This study explores the effect of 5-fluorouracil (5FU) exposure on mRNA levels of its target enzyme thymidylate synthase (TS) and the rate-limiting catabolic enzyme dihydropyrimidine dehydrogenase (DPD) in tumors of colorectal cancer patients. TS and DPD mRNA levels were determined in primary tumor and liver metastasis samples from patients who were either not pretreated (n = 29) or given one presurgery bolus of 5FU (n = 67). In both groups a wide variation in TS mRNA levels was observed. Median TS mRNA expression in 17 primary tumors of exposed patients was 3.0-fold higher than in 19 primary tumors of unexposed patients (p = 0.015). TS mRNA expression in liver metastasis samples of exposed patients (n = 16) was also higher (5.2-fold) than that of unexposed patients (n = 48; p <0.001). Also DPD mRNA express ion displayed a large degree of interpatient variation. No difference in DPD expression in liver metastasis samples was observed between exposed and unexposed patients. However, median DPD mRNA expression in 15 primary tumors of exposed patients was 3.2-fold lower than in 18 primary tumors of unexposed patients (p = 0.027). In conclusion, administration of 5FU in vivo influences the gene expression of TS and DPD.

Original languageEnglish (US)
Pages (from-to)2609-2612
Number of pages4
JournalInternational Journal of Cancer
Volume120
Issue number12
DOIs
StatePublished - Jun 15 2007
Externally publishedYes

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Keywords

  • 5-fluorouracil
  • Colorectal carcinoma
  • Dihydropyrimidine dehydrogenase
  • RT-PCR
  • Thymidylate synthase

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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