Expression of NAD(P)H:quinone oxidoreductase and glutathione S-transferases alpha and pi in human renal cell carcinoma and in kidney cancer-derived cell lines

Abstract

NAD(P)H:quinone oxidoreductase (NQOR) and glutathione S-transferases (GST) are enzymes of interest in cell defence and drug resistance. Relative levels of NQOR mRNA in renal cell carcinomas were 28 +/- 24% (n = 21) of those in non-neoplastic tissue and the enzyme activity decreased from 41 +/- 39 to 18 +/- 27 mU/mg protein (n = 23). In three of the cases, there was no measurable NQOR enzyme activity at all, indicating a polymorphism in the population for this gene. Relative GST-alpha mRNA levels in the tumours were on average 6 +/- 6% (n = 22) of the control value, whereas for GST-pi mRNA smaller decreases as well as increases were found in the tumours as compared to control tissue, but, on average, the level remained unchanged. Overall GST activity measured with CDNB as a substrate was 152 +/- 157 mU/mg protein in tumour tissue and 342 +/- 177 mU/mg protein in non-neoplastic tissue (n = 23). In all kidney tumour-derived cell lines NQOR mRNA was strongly expressed and on a per protein basis NQOR activity was about 10-fold higher than in the kidney tumour samples. GST-pi but not GST-alpha mRNA was also present. Total GST enzyme activities in these cell lines were similar to those in kidney tumour samples. HepG2 cells exhibited expression of NQOR and GST-alpha; GST-pi was not detectable. NQOR activity in HepG2 was about four-fold higher than in kidney-derived cell lines. Thus, NQOR and GST-alpha are both down-regulated in renal carcinoma, but their expression diverges in carcinoma cell lines.