title: A comprehensive examination of Smad4, Smad6 and Smad7 mRNA expression in pancreatic ductal adenocarcinoma.
abstract: BACKGROUND
  Smad4, Smad6 and Smad7 are important molecules in TGF-beta pathway, which plays an important role in pancreatic ductal adenocarcinoma (PDAC) biology. Aims : This study examined the expression profiles of Smad4, Smad6 and Smad7 mRNA in patient samples of PDAC and their relationship to Smad protein expression, SMAD4 gene mutations, clinicopathological parameters and patient survival.
  
  
  METHODS
  Surgically resected, paired normal and tumor tissues of 25 patients of PDAC were studied.
  
  
  METHODS
  Protein and mRNA levels were assessed by immunohistochemistry and RT-PCR, respectively.
  
  
  METHODS
  Statistical analysis was done using Student's t-test, Pearson's chi-square test, Spearman's Rank Correlation, Pearson's Correlation test and Kaplan-Meier Logrank test.
  
  
  RESULTS
  While there was a highly significant difference in the protein levels of all three Smads in tumor as compared to normal samples, mRNA levels were significantly different only for Smad4. Protein levels did not correlate significantly with mRNA levels for any of the three Smads. The mRNA levels of Smad4 and Smad6, Smad4 and Smad7, and Smad6 and Smad7 in tumor samples showed a significant positive correlation. The relationship of Smad4 mRNA expression to SMAD4 gene status and Smad4 protein expression was discordant and there was no significant correlation between mRNA expression and clinicopathological parameters and patient survival.
  
  
  CONCLUSIONS
  The absence of concordance between SMAD4 gene status, mRNA expression and Smad4 protein expression suggests the presence of other regulatory mechanisms in Smad4 transcription and translation in PDAC.
authors.affiliation: School of Molecular and Microbial Biosciences, The University of Sydney, NSW, 2006, Australia. puneetsingh_bio@y7mail.com
authors.forename: P
authors.initials: P
authors.lastname: Singh
authors.forename: J D
authors.initials: JD
authors.lastname: Wig
authors.forename: R
authors.initials: R
authors.lastname: Srinivasan
authors.forename: B D
authors.initials: BD
authors.lastname: Radotra
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D000328:Adult; D000368:Aged; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051901:Smad4 Protein / Q000235:genetics* / Q000378:metabolism; D051905:Smad6 Protein / Q000235:genetics* / Q000378:metabolism; D051906:Smad7 Protein / Q000235:genetics* / Q000378:metabolism; D015996:Survival Rate
chemical_list: D012333:RNA, Messenger; C497796:SMAD4 protein, human; C497802:SMAD6 protein, human; C497806:SMAD7 protein, human; D051901:Smad4 Protein; D051905:Smad6 Protein; D051906:Smad7 Protein