PURPOSE: 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. MATERIALS AND 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.
PURPOSE: 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. MATERIALS AND 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.
Authors: Heba W Z Khella; Nicole M A White; Hala Faragalla; Manal Gabril; Mina Boazak; David Dorian; Bishoy Khalil; Hany Antonios; Tian Tian Bao; Maria D Pasic; R John Honey; Robert Stewart; Kenneth T Pace; Georg A Bjarnason; Michael A S Jewett; George M Yousef Journal: Tumour Biol Date: 2011-11-16