title: Expression and clinical significance of the transforming growth factor-β signalling pathway in endometrial cancer.
abstract: OBJECTIVE
  To evaluate the components of the transforming growth factor (TGF)-β-Smad signalling pathway in human endometrial cancer (EC).
  
  
  RESULTS
  TGF-β1, TGF-β receptor type I, TGF-β receptor type II, Smad2, Smad3, Smad4, Skil and Disabled-2 (DAB2) mRNA levels were determined by reverse transcriptase polymerase chain reaction on EC cell lines and in 70 EC tissues. Immunohistochemistry for Skil and DAB2 antibodies was performed on 362 EC cases. Decreased mRNA levels of all eight components of the TGF-β pathway tested were found in the majority of 70 cases. For DAB2, the mRNA level was correlated with protein expression level (P = 0.04). The Skil mRNA level was associated with tumour stage (P = 0.03), and the Smad2/3/4 mRNA level with tumour grade (P = 0.03, P = 0.02, and P = 0.00, respectively). The Smad4 mRNA level was also associated with tumour size (P = 0.05), subtype (P = 0.04), and disease-free survival (DFS) (P = 0.05). The TGF-β1 mRNA level was associated with DFS (P = 0.04). Finally, tumours with positive Skil protein expression had a shorter recurrence time, whereas, those with positive DAB2 protein expression had a longer recurrence time.
  
  
  CONCLUSIONS
  Down-regulation of the TGF-β-Smad signalling pathway might be responsible for the pathogenesis of human EC, and some of its components appeared to be prognostic factors. Exploration of future therapy targeting the TGF-β-Smad pathway is warranted in EC.
authors.affiliation: Department of Pathology, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: Paulette
authors.initials: P
authors.lastname: Mhawech-Fauceglia
authors.affiliation: Department of Gynecologic-Oncology, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Kesterson
authors.affiliation: Department of Biostatistics, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Gynecologic-Oncology, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: Stacey
authors.initials: S
authors.lastname: Akers
authors.affiliation: Department of Gynecologic-Oncology, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: Nefertiti Chianti
authors.initials: NC
authors.lastname: DuPont
authors.affiliation: Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Clark
authors.affiliation: Department of Gynecologic-Oncology, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: Shashikant
authors.initials: S
authors.lastname: Lele
authors.affiliation: Department of Biostatistics, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: Song
authors.initials: S
authors.lastname: Liu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051017:Apoptosis Regulatory Proteins; D045744:Cell Line, Tumor; D015536:Down-Regulation; D016889:Endometrial Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D051785:Smad Proteins / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C102885:DAB2 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C060615:SKIL protein, human; D051785:Smad Proteins; D016212:Transforming Growth Factor beta; D025521:Tumor Suppressor Proteins