Expression of cyclooxygenase-1 and -2 in urinary bladder carcinomas in vivo and in vitro and prostaglandin E2 synthesis in cultured bladder cancer cells.
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 Cox-1 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 Cox-2 expression and tumour differentiation or stage of invasion. We also evaluated the mRNA expression of Cox-1 and Cox-2 and synthesis of prostaglandin E2 (PGE2) 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 PGE2 synthesis in these cell lines. Indomethacin inhibited the synthesis of PGE2 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.
Boström
P J
PJ
Department of Surgery, Turku University Central Hospital, Finland.
Aaltonen
V
V
Söderström
K O
KO
Uotila
P
P
Laato
M
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D007213:Indomethacin / Q000494:pharmacology; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D012334:RNA, Neoplasm / Q000032:analysis; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology
D007527:Isoenzymes; D008565:Membrane Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D007213:Indomethacin