title: Sodium arsenite-induced abnormalities in expressions of Caveolin-1, eNOS, IKKβ, and COX-2 in SV-40 immortalized human uroepithelial cells and in urothelial carcinomas.
abstract: Arsenic, a known human carcinogen, is found throughout the crust of the earth. Prolonged arsenic exposure is a known cause of urothelial carcinoma (UC) and blackfoot disease (BFD). The aim of this study was to determine the effect of sodium arsenite on Caveolin-1 and downstream signaling molecules (eNOS, IKKβ and COX-2) expression in human urothelial cells (SV-HUC-1). Immunohistochemical (IHC) staining of Caveolin-1, eNOS, IKKβ, and COX-2 was also compared between UC patients from endemic and non-endemic areas of BFD in Taiwan. Immunocytochemical staining and Western blotting results revealed increased expression of Caveolin-1, IKKβ, and COX-2 but decreased eNOS in SV-HUC-1 cells treated with low concentration of arsenite. Additionally, MEK inhibitor (U0126) significantly attenuated arsenite-induced expression of Caveolin-1, IKKβ and COX-2 while reducing eNOS expression. The IHC staining of UCs revealed that expressions of Caveolin-1, IKKβ, and COX-2 were significantly higher in patients from endemic areas of BFD compared to patients from non-endemic areas (p=0.011, p=0.002, p=0.0001) whereas eNOS was significantly lower (p=0.0001). The correlation observed between Caveolin-1 and downstream signaling molecule expression may be an important mechanism of arsenic-induced urothelial carcinogenesis.
authors: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors: Xuan-Ping
authors: XP
authors: Liu
authors: Ya-Chun
authors: YC
authors: Huang
authors: Wen-Chun
authors: WC
authors: Hung
authors: Wan-Tzu
authors: WT
authors: Chen
authors: Hsin-Su
authors: HS
authors: Yu
authors: Chee-Yin
authors: CY
authors: Chai
mesh_terms: D018053:Arsenites / Q000494:pharmacology*; D002273:Carcinogens / Q000633:toxicity*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000378:metabolism; D051242:Caveolin 1 / Q000378:metabolism*; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D015398:Signal Transduction; D013539:Simian virus 40; D017670:Sodium Compounds / Q000494:pharmacology*; D014571:Urologic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D019459:Urothelium / Q000187:drug effects* / Q000378:metabolism
chemical_list: D018053:Arsenites; C495540:CAV1 protein, human; D002273:Carcinogens; D051242:Caveolin 1; D017670:Sodium Compounds; C017947:sodium arsenite; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D051550:I-kappa B Kinase; C496560:IKBKB protein, human