Significance of thymidine kinase activity in renal cell carcinoma.
OBJECTIVE
Thymidine kinase (TK) has a key role in the complementary or alternative salvage pathway of pyrimidine synthesis. Little is known about the significance of TK activity in renal cell carcinoma. We examined the activity of TK in 66 renal cell carcinomas and investigated the association of the level of TK activity with the stage and grade of renal cell carcinoma.


METHODS
TK activity in nonfixed, fresh frozen renal cell carcinoma and normal kidney was determined by the DEAE cellulose disc method.


RESULTS
The activity of TK was approximately 4-fold higher in normal kidney compared with renal cell carcinoma. The higher the stage and grade of renal cell carcinoma, the higher the TK activity. TK activity correlated positively with the activity of thymidine synthase, which is a key enzyme for pyrimidine synthesis in the de novo pathway. TK activity in renal cell carcinoma cells was inversely related to their sensitivity to 5-fluorouracil.


CONCLUSIONS
To our knowledge this report represents the first study to demonstrate that the level of TK activity correlates with the stage and grade of renal cell carcinoma, and higher TK activity in renal cell carcinoma predicts lower sensitivity to 5-fluorouracil. These results suggest that high TK activity may be associated with the malignant potential of renal cell carcinoma and TK may be a molecular therapeutic target for this disease. In addition, the combination of TK and thymidylate synthase inhibitors may be beneficial for renal cell carcinoma.
Mizutani
Yoichi
Y
Department of Urology, Kyoto Prefectural University of Medicine, Japan.
Wada
Hiromi
H
Yoshida
Osamu
O
Fukushima
Masakazu
M
Nakao
Masahiro
M
Miki
Tsuneharu
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002292:Carcinoma, Renal Cell / Q000201:enzymology*; D005260:Female; D006801:Humans; D007668:Kidney / Q000201:enzymology; D007680:Kidney Neoplasms / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D013937:Thymidine Kinase / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D013937:Thymidine Kinase