title: The expression of TGF-β1, Smad3, phospho-Smad3 and Smad7 is correlated with the development and invasion of nonfunctioning pituitary adenomas.
abstract: BACKGROUND
  Transforming growth factor β (TGF-β) signaling functions as a suppressor or a promoter in tumor development, depending on the tumor stage and type. However, the role of TGF-β signaling in nonfunctioning pituitary adenomas (NFPAs) has not been explored.
  
  
  METHODS
  TGF-β1, Smad2, phospho-Smad2 (p-Smad2), Smad3, phospho-Smad3 (p-Smad3), Smad4, and Smad7 were detected in 5 cases of normal anterior pituitaries, 29 cases of invasive NFPAs, and 21 cases of noninvasive NFPAs by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR), Western blot, and immunohistochemical analysis.
  
  
  RESULTS
  The Smad3 and p-Smad3 protein levels gradually decreased from normal anterior pituitaries, noninvasive NFPAs, to invasive NFPAs. However, there were no significant differences in Smad2 (P = 0.122) and p-Smad2 protein levels (P = 0.101) or Smad2 mRNA level (P = 0.409). In addition, the TGF-β1 mRNA level gradually decreased while the Smad7 mRNA level gradually increased from normal anterior pituitaries, noninvasive NFPAs, to invasive NFPAs. Furthermore, proliferating cell nuclear antigen (PCNA) mRNA level was markedly increased in invasive NFPAs compared to noninvasive ones (P < 0.01), and its level was negatively correlated with Smad3 mRNA level (P < 0.01).
  
  
  CONCLUSIONS
  The activity of TGF-β signaling may be restrained in NFPAs and is correlated with the development and invasion of NFPAs.
authors.forename: Li
authors.initials: L
authors.lastname: Zhenye
authors.forename: Li
authors.initials: L
authors.lastname: Chuzhong
authors.forename: Wu
authors.initials: W
authors.lastname: Youtu
authors.forename: Lan
authors.initials: L
authors.lastname: Xiaolei
authors.forename: Cao
authors.initials: C
authors.lastname: Lei
authors.forename: Hong
authors.initials: H
authors.lastname: Lichuan
authors.forename: Wang
authors.initials: W
authors.lastname: Hongyun
authors.forename: Wu
authors.initials: W
authors.lastname: Yonggang
authors.forename: Wang
authors.initials: W
authors.lastname: Fei
authors.affiliation: Beijing Neurosurgical Institute, Capital Medical University, Beijing 100050, China. zyz2004520@yeah.net.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Yazhuo
mesh_terms: D000236:Adenoma / Q000235:genetics* / Q000473:pathology*; D000328:Adult; D000368:Aged; D015153:Blotting, Western; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010766:Phosphorylation; D010911:Pituitary Neoplasms / Q000235:genetics* / Q000473:pathology*; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051899:Smad2 Protein / Q000235:genetics / Q000378:metabolism; D051900:Smad3 Protein / Q000235:genetics* / Q000378:metabolism; D051906:Smad7 Protein / Q000235:genetics* / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000235:genetics* / Q000378:metabolism
chemical_list: D018809:Proliferating Cell Nuclear Antigen; C497782:SMAD2 protein, human; C497790:SMAD3 protein, human; C497806:SMAD7 protein, human; D051899:Smad2 Protein; D051900:Smad3 Protein; D051906:Smad7 Protein; D053773:Transforming Growth Factor beta1