title: Inducible nitric oxide synthase and PPARγ are involved in bladder cancer progression.
abstract: OBJECTIVE
  We evaluated the role of inducible nitric oxide synthase and PPARγ as prognostic factors for bladder cancer.
  
  
  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.
authors: Research Area, Institute of Oncology Angel H. Roffo, University of Buenos Aires, Buenos Aires, Argentina.
authors: Eduardo Omar
authors: EO
authors: Sandes
authors: Catalina
authors: C
authors: Lodillinsky
authors: Yanina
authors: Y
authors: Langle
authors: Denise
authors: D
authors: Belgorosky
authors: Lina
authors: L
authors: Marino
authors: Liliana
authors: L
authors: Gimenez
authors: Alberto Ricardo
authors: AR
authors: Casabé
authors: Ana María
authors: AM
authors: Eiján
mesh_terms: D000818:Animals; D018450:Disease Progression; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D052247:Nitric Oxide Synthase Type II / Q000502:physiology*; D047495:PPAR gamma / Q000502:physiology*; D011379:Prognosis; D001749:Urinary Bladder Neoplasms / Q000209:etiology* / Q000473:pathology
chemical_list: D047495:PPAR gamma; D052247:Nitric Oxide Synthase Type II