title: TGF-beta signaling is disrupted in endometrioid-type endometrial carcinomas.
abstract: OBJECTIVE
  Previous studies have demonstrated deregulation of the expression and changes in the intracellular distribution of TGF-beta pathway components in human endometrial cancer (EC). The aim of this study was to assess the relationship between the expression of TGF-beta cascade components, including TGF-beta receptor type I (TGF beta RI) and type II (TGF beta RII), SMAD2, SMAD3, SMAD4, and clinicopathological features--tumor grade, FIGO classification, and depth of myometrial invasion--of type I (endometrioid-type) ECs to give some insight into the role of TGF-beta cascade components in endometrial tumorigenesis.
  
  
  METHODS
  The expression of TGF beta RI, TGF beta RII, SMAD2, SMAD3, and SMAD4 was evaluated both at the mRNA and protein level using reverse transcription polymerase chain reaction (RT-PCR) and ELISA, respectively.
  
  
  RESULTS
  Infiltrating endometrial carcinomas (less and more than half of the myometrial wall thickness) express significantly higher TGF beta RII protein level compared with non-infiltrating tumors (P = 0.04 and P = 0.01, respectively). Decreased level of SMAD2 and SMAD4 mRNAs was observed in the uterine tumors infiltrating less and more than half of the myometrial wall (P = 0.03 and P = 0.02, respectively) compared with noninfiltrating ECs. Significantly higher SMAD4 protein level in the cytoplasmic fraction of ECs was found when tumor grade and depth of myometrial invasion were considered (P < 0.05). Generally, tumor progression was associated with a decreased number of cases characterized by the presence of SMADs in the nuclear fraction only.
  
  
  CONCLUSIONS
  Our data suggest that disturbances of the TGF beta RII and SMAD4 expression as well as localization of SMADs may be important to the infiltration of the myometrial wall by the type I endometrial carcinomas.
authors.affiliation: Department of Cytobiochemistry, University of Lodz, 90-237 Lodz, Poland. kalaiste@poczta.wp.pl
authors.forename: Dagmara
authors.initials: D
authors.lastname: Piestrzeniewicz-Ulanska
authors.forename: Magdalena
authors.initials: M
authors.lastname: Brys
authors.forename: Andrzej
authors.initials: A
authors.lastname: Semczuk
authors.forename: Tomasz
authors.initials: T
authors.lastname: Rechberger
authors.forename: Jerzy A
authors.initials: JA
authors.lastname: Jakowicki
authors.forename: Wanda M
authors.initials: WM
authors.lastname: Krajewska
mesh_terms: D030201:Activin Receptors, Type I / Q000096:biosynthesis / Q000235:genetics; D018269:Carcinoma, Endometrioid / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D016889:Endometrial Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D051899:Smad2 Protein; D051900:Smad3 Protein; D051901:Smad4 Protein; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000502:physiology*
chemical_list: D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; C497782:SMAD2 protein, human; C497790:SMAD3 protein, human; C497796:SMAD4 protein, human; D051899:Smad2 Protein; D051900:Smad3 Protein; D051901:Smad4 Protein; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II