title: Transforming growth factor β repressor, SnoN, is overexpressed in human gastrointestinal stromal tumors.
abstract: OBJECTIVE
  The transforming growth factor bgr; (TGF-β)/ Smad pathway is implicated in the development of interstitial cells of Cajal. The aim of this study was to examine the role of this pathway in human gastrointestinal stromal tumors (GISTs).
  
  
  METHODS
  The expression of TGF-β receptor II (TβRII), phosphorylated Smad2 (p-Smad2), SnoN, p21(WAF17sol;CIP1) and p27(KIP1) was examined by immunohistochemistry in 30 hu-man GISTs in relation to prognostic factors.
  
  
  RESULTS
  TβRII was expressed in 76.9% of the cases. All cases were positive for p-Smad2 and SnoN, with significantly higher expression levels in small intestinal compared to gastric GISTs. Downregulation of p21(WAF1/CIP1) and p27(KIP1) was found in 78.6% and 46.4% of the cases respectively, while cytoplasmic expression of p27(KIP1) was also noted in 50% of GISTs.
  
  
  CONCLUSIONS
  TGF-β/Smad pathway may contribute to GIST pathogenesis. SnoN overexpression and low levels of p21(WAF1)/CIP1 and p27(KIP1) may be of importance in GISTs.
authors: Department of Pathology, General Hospital of Patras, Agios Andreas, Patras, Greece. vibra@upatras.gr
authors: V
authors: V
authors: Bravou
authors: P
authors: P
authors: Papanastasopoulos
authors: D
authors: D
authors: Verras
authors: I
authors: I
authors: Kotsikogianni
authors: V
authors: V
authors: Damaskou
authors: M
authors: M
authors: Repanti
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002272:Carcinoembryonic Antigen / Q000097:blood; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000032:analysis; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000032:analysis; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000737:chemistry* / Q000209:etiology; D046152:Gastrointestinal Stromal Tumors / Q000737:chemistry* / Q000209:etiology; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D017346:Protein Serine-Threonine Kinases / Q000032:analysis; D011518:Proto-Oncogene Proteins / Q000032:analysis* / Q000502:physiology; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000032:analysis; D051899:Smad2 Protein / Q000032:analysis
chemical_list: C493956:CDKN1A protein, human; C436291:CDKN1B protein, human; D002272:Carcinoembryonic Antigen; D050759:Cyclin-Dependent Kinase Inhibitor p21; D047908:Intracellular Signaling Peptides and Proteins; D011518:Proto-Oncogene Proteins; D018125:Receptors, Transforming Growth Factor beta; C060615:SKIL protein, human; C497782:SMAD2 protein, human; D051899:Smad2 Protein; D050760:Cyclin-Dependent Kinase Inhibitor p27; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II