Background: Orotate phosphoribosyl transferase (OPRT) is the initial key enzyme in the 5-FU metabolic pathway. It is an enzyme that converts 5-fluorouracil into 5-fluorouridine monophosphate. We have previously shown that there is a strong positive correlation between OPRT activity and the antitumor effects of 5-FU. In this study, we investigated the correlation between OPRT activity and mRNA expression levels of OPRT in 10 colorectal tumors.
Methods: Activity was measured by radioassay in tissues. mRNA expression levels (OPRT/beta-actin) were measured by TaqMan PCR assay in the same tissues.
Results: There was no correlation between OPRT activity and mRNA expression levels (r = -0.4301, p = 0.8926).
Discussion: The absolute amount of an enzyme is determined by speed of synthesis (kappa s) and degradation (kappa deg). OPRT is thought to be a constitutive enzyme, and the results of this study show that it is difficult to estimate the OPRT activity from mRNA expression levels.
Conclusions: Further studies are necessary to develop techniques to measure OPRT activity in biopsies, in order to establish tailor-made therapies based on estimating the antitumor effect of 5-FU from OPRT, an enzyme related to 5-FU metabolism.