[Correlation between enzymatic activity and gene expression of orotate phosphoribosyl transferase (OPRT) in colorectal cancer].

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.