Abstract
Cyclooxygenases (Coxs) are the rate-limiting enzymes catalysing the formation of prostaglandins, which are involved in various of physiological processes. Increased Cox-2 expression has been observed in several malignancies, but the exact role of Cox-2 in carcinogenesis remains unsolved. We studied the expression of both Cox1 and Cox-2 by immunohistochemistry in 29 transitional cell carcinomas of the urinary bladder. Diffuse cytoplasmic immunosignal for Cox-2 was detected in all cancer specimens. The expression was moderate in 55% and strong in 31% of the carcinomas. The normal urothelium in the samples stained also for Cox-2, but the intensity of the immunosignal was weak in most specimens. Cox-1 was expressed in the stroma of bladder wall, whereas in the tumour cells, Cox-1 immunosignal was either absent or weak. No correlation was detected between Cox-1 or Cox2 expression and tumour differentiation or stage of invasion. We also evaluated the mRNA expression of Cox1 and Cox-2 and synthesis of prostaglandin E 2 (PGE 2 ) in three bladder carcinoma cell lines (RT4, 5637, and T24). All cell lines expressed high levels of Cox-2 mRNA, whereas Cox-1 mRNA expression was detected only in T24 cells. There was great variation in the basal levels of PGE 2 synthesis in these cell lines. Indomethacin inhibited the synthesis of PGE 2 in all three cell lines, although the level of Cox-2 mRNA tended to increase by indomethacin. These results indicate that Cox-2 is widely expressed in human bladder carcinomas and that the role of Cox-2 inhibition in bladder cancer should be further studied.