Clutathione S-transferase T1-1 activity upregulated in transitional cell carcinoma of urinary bladder

Objectives. To perform a systematic functional investigation of different glutathione S-transferase (GST) classes, including GST class Theta (GSTT) member GSTT1-1, in transitional cell carcinoma (TCC) and the surrounding normal uroepithelium of the same individuals. Recently, it was suggested that GSTT1-1 might be an important risk modulator for TCC. Methods. Tumor samples and surrounding normal uroepithelium were obtained from 24 patients with TCC of urinary bladder. The following substrates with differential specificities were used: 1-chloro-2,4-dinitrobenzene for overall CST activity; 7-chloro-4-nitrobenzo-,2-oxa-1,3-diazole for CST Alpha; 1,2-dichloro-4nitro-benzene for CST Mu; 4-vinylpyridine for CST Pi 1 -1 (GSTPI -1); and 1,2-epoxy-3-(p-nitrophenoxy) propane for GSTT1- 1. Results. GSTPI -1 and GSTT1 -1 activities were demonstrated in all uroepithelial and TCC samples, and CST Mu activity was detectable in 1 1 of 24 patients. In the tumor specimens, significant upregulation of all expressed CST subtypes was observed. The mean GSTP1-1 and GSTT1-1 level in TCC was increased 2-fold and 3.6-fold, respectively, compared with the mean level in the normal uroepithelium (P < 0.001). Tumor GSTT1 -1 activities correlated statistically significantly with the tumor stage (P < 0.05). Conclusions. In tumors and adjacent normal uroepithelium of patients with TCC, three major cytosolic CST classes, Mu, Pi, and Theta, were expressed. Although the CST isoenzyme pattern in TCC was similar to that of the corresponding normal uroepithelium, during cancer progression a clear tendency toward an increase in all the CST subtypes expressed was noted. For the first time, distinct GSTT1 -1 activity levels were demonstrated in human uroepithelium, as well as its pronounced upregulation in TCC. (c) 2005 Elsevier Inc.