title: Elevated prostaglandin E2 level via cPLA2--COX-2--mPGES-1 pathway involved in bladder carcinogenesis induced by terephthalic acid-calculi in Wistar rats.
abstract: To investigate the prostaglandin E2 (PGE2) biosynthetic mechanism in bladder carcinogenesis, we established Wistar rat model of bladder papilloma and transitional cell carcinoma (TCC) induced by 5% terephthalic acid (TPA) treatment. Then, the mRNA level of cytosolic phospholipase A2 (cPLA2), cyclooxygenases (COX)-1 and -2, membrane-bound PGE2 synthases (mPGES)-1 and -2 was detected using reverse transcription polymerase chain reaction (RT-PCR). Immunoblotting was applied to detect the expression of COX-2 protein. Proliferating cell nuclear antigen (PCNA) was determined by immunohistochemistry. In addition, the level of PGE2 was measured by radioimmunoassay (RIA). Bladder papilloma (100%, 8/8) was examined in rats after 24-week treatment, and bladder TCC (80%, 16/20) was found after 48-week treatment. Histopathological changes were not found in control group rats. The incidence of bladder papilloma and TCC in test group was significantly higher than that in control group (P<0.01). The mRNA levels of cPLA2, COX-2 and mPGES-1 in the bladder papilloma and TCC were significantly higher than those in normal bladder (P<0.01), while the mRNA levels of COX-1 and mPGES-2 in TCC were unchanged compared with normal bladder. Bladder TCC exhibited a substantial expression of COX-2 protein. On the contrary, normal bladder tissue barely expresses COX-2 protein. PCNA labeling index (LI) and the level of PGE2 in bladder papilloma are much higher than those in normal bladder (P<0.01), but lower than those in bladder TCC (P<0.05). In conclusion, increasing PGE2 level via cPLA2--COX-2--mPGES-1 pathway may play an important role in rat bladder carcinogenesis. PGE2 may be a biomarker for the development of bladder TCC. cPLA2 and mPGES-1 may be targets for development of novel chemoprevention strategies for bladder TCC.
authors.affiliation: Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Shi
authors.forename: Lunbiao
authors.initials: L
authors.lastname: Cui
authors.forename: Guidong
authors.initials: G
authors.lastname: Dai
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Chen
authors.forename: Hongxing
authors.initials: H
authors.lastname: Pan
authors.forename: Ling
authors.initials: L
authors.lastname: Song
authors.forename: Senping
authors.initials: S
authors.lastname: Cheng
authors.forename: Xinru
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002295:Carcinoma, Transitional Cell / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism*; D054513:Group IV Phospholipases A2; D007150:Immunohistochemistry; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D010212:Papilloma / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D010741:Phospholipases A / Q000235:genetics / Q000378:metabolism*; D054467:Phospholipases A2; D010795:Phthalic Acids / Q000633:toxicity*; D000071876:Prostaglandin-E Synthases; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D001744:Urinary Bladder Calculi / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*
chemical_list: D007527:Isoenzymes; D010795:Phthalic Acids; C011363:terephthalic acid; D051546:Cyclooxygenase 2; D010741:Phospholipases A; D054513:Group IV Phospholipases A2; D054467:Phospholipases A2; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases; D015232:Dinoprostone