title: Enhanced GSTP1 expression in transitional cell carcinoma of urinary bladder is associated with altered apoptotic pathways.
abstract: OBJECTIVE
  Glutathione S-transferase P1 (GSTP1) provides an important link between activity of regulatory stress kinases and apoptotic pathways. It can be hypothesized that up-regulated GSTP1, in TCC, might enhance apoptosis inhibition. We aimed to establish whether relationship between GSTP1 expression and executive (pro-caspase 3, cleaved caspase 3) and regulatory (Bcl-2) apoptotic pathways in TCC exists.
  
  
  METHODS
  Samples were obtained from 84 TCC patients (41 consecutive patient with muscle noninvasive and 43 consecutive patients with muscle invasive TCC tumors), who underwent surgery at the Institute of Urology and Nephrology, Clinical Centre of Serbia, during 2006 and 2007. Expression of GSTP1, pro-caspase 3 (CPP32), and Bcl-2, as well as cleaved caspase-3 labeling index (LI) were determined by immunocytochemistry. Levels of expression were correlated with tumor stage, grade, and invasiveness.
  
  
  RESULTS
  GSTP1 protein expression was demonstrated in all tumor samples examined. According to GSTP1 status, all tumors were divided into groups with low, moderate, or high GSTP1 status. Expression of CPP32 and cleaved caspase 3 was positive in 80% of TCC patients. Their levels differed significantly between groups with various GSTP1 expression (P < 0.05), with the lowest CPP32 expression and cleaved caspase 3 LI in tumors with high GSTP1 status. Moreover, significant negative correlation was found between GSTP1 level and cleaved caspase 3 LI (r = -0.459, P = 0.041). The positive rate of Bcl-2 protein expression was 48%. Most of the Bcl-2 positive patients exhibited at the same time high GSTP1 positivity (P = 0.078). Significant association with tumor grade and stage was found for all examined parameters except for CPP32 regarding tumor grade.
  
  
  CONCLUSIONS
  Based on results obtained, we conclude that enhanced GSTP1 expression in TCC of urinary bladder is associated with altered apoptotic pathways. Molecular interplay between GSTP1 and members of apoptotic cascade might, at least partially, play a role in development of invasive characteristics of TCC.
authors.affiliation: Institute of Medical and Clinical Biochemistry, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Marija
authors.initials: M
authors.lastname: Pljesa-Ercegovac
authors.forename: Ana
authors.initials: A
authors.lastname: Savic-Radojevic
authors.forename: Dejan
authors.initials: D
authors.lastname: Dragicevic
authors.forename: Jasmina
authors.initials: J
authors.lastname: Mimic-Oka
authors.forename: Marija
authors.initials: M
authors.lastname: Matic
authors.forename: Tatjana
authors.initials: T
authors.lastname: Sasic
authors.forename: Tatjana
authors.initials: T
authors.lastname: Pekmezovic
authors.forename: Aleksandar
authors.initials: A
authors.lastname: Vuksanovic
authors.forename: Tatjana
authors.initials: T
authors.lastname: Simic
mesh_terms: D017209:Apoptosis; D002295:Carcinoma, Transitional Cell / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D053148:Caspase 3 / Q000378:metabolism; D005260:Female; D051549:Glutathione S-Transferase pi / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D019042:Muscle Neoplasms / Q000378:metabolism* / Q000473:pathology; D009361:Neoplasm Invasiveness; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; C505407:CASP3 protein, human; D053148:Caspase 3