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Inducible Nitric Oxide Synthase and PPARγ are Involved in Bladder Cancer Progression

2012; Lippincott Williams & Wilkins; Volume: 188; Issue: 3 Linguagem: Inglês

10.1016/j.juro.2012.04.099

1527-3792

Eduardo Sandes, Catalina Lodillinsky, Yanina Langle, Denise Belgorosky, Lina Marino, Liliana Giménez, Alberto Ricardo Casabé, Ana María Eiján,

Nitric Oxide and Endothelin Effects

No AccessJournal of UrologyInvestigative Urology1 Sep 2012Inducible Nitric Oxide Synthase and PPARγ are Involved in Bladder Cancer Progression Eduardo Omar Sandes, Catalina Lodillinsky, Yanina Langle, Denise Belgorosky, Lina Marino, Liliana Gimenez, Alberto Ricardo Casabé, and Ana María Eiján Eduardo Omar SandesEduardo Omar Sandes Research Areas, Institute of Oncology Angel H. Roffo, University of Buenos Aires, Buenos Aires, Argentina , Catalina LodillinskyCatalina Lodillinsky Research Areas, Institute of Oncology Angel H. Roffo, University of Buenos Aires, Buenos Aires, Argentina , Yanina LangleYanina Langle Research Areas, Institute of Oncology Angel H. Roffo, University of Buenos Aires, Buenos Aires, Argentina , Denise BelgoroskyDenise Belgorosky Research Areas, Institute of Oncology Angel H. Roffo, University of Buenos Aires, Buenos Aires, Argentina , Lina MarinoLina Marino Diagnostic Areas, Institute of Oncology Angel H. Roffo, University of Buenos Aires, Buenos Aires, Argentina , Liliana GimenezLiliana Gimenez Diagnostic Areas, Institute of Oncology Angel H. Roffo, University of Buenos Aires, Buenos Aires, Argentina , Alberto Ricardo CasabéAlberto Ricardo Casabé Surgical Areas, Institute of Oncology Angel H. Roffo, University of Buenos Aires, Buenos Aires, Argentina , and Ana María EijánAna María Eiján Research Areas, Institute of Oncology Angel H. Roffo, University of Buenos Aires, Buenos Aires, Argentina View All Author Informationhttps://doi.org/10.1016/j.juro.2012.04.099AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: We evaluated the role of inducible nitric oxide synthase and PPARγ as prognostic factors for bladder cancer. Materials and Methods: Inducible nitric oxide synthase and PPARγ were evaluated by Western blot and immunohistochemistry in a mouse bladder cancer model of nonmuscle invasive and invasive MB49-I tumor cells, and in human bladder cancer samples. Results: Inducible nitric oxide synthase expression was negative in mouse normal urothelium and higher in invasive than in noninvasive MB49 tumors. In vitro inducible nitric oxide synthase activity, determined as nitrite, was higher in MB49-I than in MB49 cells (p <0.001). In human samples expression was also associated with tumor invasion. Nuclear PPARγ expression was negative in normal mouse urothelium but higher in nonmuscle invasive MB49 than in MB49-I tumors. Similarly in human tumors low PPARγ was associated with poor prognosis factors, such as high histological grade (p = 0.0160) and invasion status (p = 0.0352). A positive correlation was noted between inducible nitric oxide synthase and PPARγ in low histological grade and nonmuscle invasive tumors (Pearson correlation index 0.6368, p = 0.0351, 0.4438 and 0.0168, respectively). As determined by gene reporter assay, PPARγ activity was induced by nitric oxide only in nonmuscle invasive MB49 cells (p <0.001). Conclusions: Results suggest that increased PPARγ controls inducible nitric oxide synthase expression at early tumor stages. However, regulation is lost at advanced tumor stages, when the increase in inducible nitric oxide synthase and the decrease in PPARγ seem to be associated with bladder cancer progression. References 1 : Cancer statistics, 2006. CA Cancer J Clin2006; 56: 106. Google Scholar 2 : Urothelial tumorigenesis: a tale of divergent pathways. Nat Rev Cancer2005; 5: 713. Google Scholar 3 : Molecular subtypes of bladder cancer: Jekyll and Hyde or chalk and cheese?. Carcinogenesis2006; 27: 361. 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Volume 188Issue 3September 2012Page: 967-973 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.Keywordsnitric oxide synthase type IIurinary bladderurinary bladder neoplasmsdisease progressionPPAR gammaAcknowledgmentsMaría Sol Umerez provided technical assistance.MetricsAuthor Information Eduardo Omar Sandes Research Areas, Institute of Oncology Angel H. Roffo, University of Buenos Aires, Buenos Aires, Argentina More articles by this author Catalina Lodillinsky Research Areas, Institute of Oncology Angel H. Roffo, University of Buenos Aires, Buenos Aires, Argentina Financial interest and/or other relationship with Consejo Nacional de Investigaciones Científicas y Técnicas. More articles by this author Yanina Langle Research Areas, Institute of Oncology Angel H. Roffo, University of Buenos Aires, Buenos Aires, Argentina Financial interest and/or other relationship with Consejo Nacional de Investigaciones Científicas y Técnicas. More articles by this author Denise Belgorosky Research Areas, Institute of Oncology Angel H. Roffo, University of Buenos Aires, Buenos Aires, Argentina Financial interest and/or other relationship with Consejo Nacional de Investigaciones Científicas y Técnicas. More articles by this author Lina Marino Diagnostic Areas, Institute of Oncology Angel H. Roffo, University of Buenos Aires, Buenos Aires, Argentina More articles by this author Liliana Gimenez Diagnostic Areas, Institute of Oncology Angel H. Roffo, University of Buenos Aires, Buenos Aires, Argentina More articles by this author Alberto Ricardo Casabé Surgical Areas, Institute of Oncology Angel H. Roffo, University of Buenos Aires, Buenos Aires, Argentina More articles by this author Ana María Eiján Research Areas, Institute of Oncology Angel H. Roffo, University of Buenos Aires, Buenos Aires, Argentina Financial interest and/or other relationship with Consejo Nacional de Investigaciones Científicas y Técnicas. 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