title: SnoN expression is differently regulated in microsatellite unstable compared with microsatellite stable colorectal cancers.
abstract: BACKGROUND
  SnoN is an important regulator of the transforming growth factor beta (TGFbeta) signalling pathway and has been shown to exhibit both tumour promotion and suppression activity.
  
  
  METHODS
  To further explore the role of this complex molecule in colorectal tumorigenesis, we examined 52 paired normal and tumour colorectal specimens stratified by level of microsatellite instability; 18 with high-level microsatellite instability (MSI-H) and 34 microsatellite stable (MSS). SnoN transcript expression was quantitated by real-time PCR and analysed with respect to clinical indicators of prognosis.
  
  
  RESULTS
  Within the MSI-H subgroup, SnoN was commonly either up-regulated (6/18, 33%) or down-regulated (7/18, 39%). A significantly different distribution of SnoN expression was observed in MSS cancers compared with MSI-H (P < or = 0.001). Whilst 17/34 (50%) of MSS tumours demonstrated up-regulation, none showed down-regulated expression. Within the MSI-H subgroup, up-regulation was significantly correlated with lack of repeat tract mutation in the TGFbetaRII gene (P < or = 0.025), suggesting that SnoN is more frequently up-regulated in the presence of functional TGFbeta signalling.
  
  
  CONCLUSIONS
  Together these data support the notion that SnoN has both oncogenic and tumour suppressive properties depending on other genetic changes within the tumour, and that the MSI-H pathway of colorectal tumorigenesis presents an excellent model for the study of these opposing functions.
authors.affiliation: The Conjoint Gastroenterology Laboratory, Royal Brisbane and Women's Hospital Foundation Clinical Research Centre and the Queensland Institute of Medical Research, Brisbane, 4029, Australia. June.Chia@qimr.edu.au
authors.forename: June A
authors.initials: JA
authors.lastname: Chia
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Simms
authors.forename: Sarah-Jane
authors.initials: SJ
authors.lastname: Cozzi
authors.forename: Joanne
authors.initials: J
authors.lastname: Young
authors.forename: Jeremy R
authors.initials: JR
authors.lastname: Jass
authors.forename: Michael D
authors.initials: MD
authors.lastname: Walsh
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Spring
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Leggett
authors.forename: Vicki L J
authors.initials: VL
authors.lastname: Whitehall
mesh_terms: D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D043243:DNA Sequence, Unstable / Q000235:genetics / Q000502:physiology*; D004273:DNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics / Q000502:physiology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D018895:Microsatellite Repeats / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*
chemical_list: D004273:DNA, Neoplasm; D047908:Intracellular Signaling Peptides and Proteins; D011518:Proto-Oncogene Proteins; C060615:SKIL protein, human