title: Stromal upregulation of lateral epithelial adhesions: gene expression analysis of signalling pathways in prostate epithelium.
abstract: BACKGROUND
  Stromal signalling increases the lateral cell adhesions of prostate epithelial cells grown in 3D culture. The aim of this study was to use microarray analysis to identify significant epithelial signalling pathways and genes in this process.
  
  
  METHODS
  Microarray analysis was used to identify genes that were differentially expressed when epithelial cells were grown in 3D Matrigel culture with stromal co-culture compared to without stroma. Two culture models were employed: primary epithelial cells (ten samples) and an epithelial cell line (three experiments). A separate microarray analysis was performed on each model system and then compared to identify tissue-relevant genes in a cell line model.
  
  
  RESULTS
  TGF beta signalling was significantly ranked for both model systems and in both models the TGF beta signalling gene SOX4 was significantly down regulated. Analysis of all differentially expressed genes to identify genes that were common to both models found several morphology related gene clusters; actin binding (DIAPH2, FHOD3, ABLIM1, TMOD4, MYH10), GTPase activator activity (BCR, MYH10), cytoskeleton (MAP2, MYH10, TMOD4, FHOD3), protein binding (ITGA6, CD44), proteinaceous extracellular matrix (NID2, CILP2), ion channel/ ion transporter activity (CACNA1C, CACNB2, KCNH2, SLC8A1, SLC39A9) and genes associated with developmental pathways (POFUT1, FZD2, HOXA5, IRX2, FGF11, SOX4, SMARCC1).
  
  
  CONCLUSIONS
  In 3D prostate cultures, stromal cells increase lateral epithelial cell adhesions. We show that this morphological effect is associated with gene expression changes to TGF beta signalling, cytoskeleton and anion activity.
authors.affiliation: Yorkshire Cancer Research Unit, Dept, Biology, University of York, Heslington, York YO10 5YW, UK.
authors.forename: Karen F
authors.initials: KF
authors.lastname: Chambers
authors.forename: Joanna F
authors.initials: JF
authors.lastname: Pearson
authors.forename: Davide
authors.initials: D
authors.lastname: Pellacani
authors.forename: Naveed
authors.initials: N
authors.lastname: Aziz
authors.forename: Miodrag
authors.initials: M
authors.lastname: Gužvić
authors.forename: Christoph A
authors.initials: CA
authors.lastname: Klein
authors.forename: Shona H
authors.initials: SH
authors.lastname: Lang
mesh_terms: D018929:Cell Culture Techniques; D002460:Cell Line; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D008297:Male; D046228:Microarray Analysis; D009024:Morphogenesis; D011467:Prostate / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D055751:SOXC Transcription Factors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D017154:Stromal Cells / Q000166:cytology* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C083431:SOX4 protein, human; D055751:SOXC Transcription Factors; D016212:Transforming Growth Factor beta