Stromal upregulation of lateral epithelial adhesions : gene expression analysis of signalling pathways in prostate epithelium

Chambers, Karen F., Pearson, Joanna F, Pellacani, Davide, Aziz, Naveed, Gužvić, Miodrag, Klein, Christoph A, & Lang, Shona H (2011) Stromal upregulation of lateral epithelial adhesions : gene expression analysis of signalling pathways in prostate epithelium. Journal of Biomedical Science, 18(1), p. 45.

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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.

Impact and interest:

8 citations in Scopus
6 citations in Web of Science®
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ID Code: 55853
Item Type: Journal Article
Refereed: Yes
Keywords: Prostate, E-cadherin, Stroma, 3D-culture, Spheroids
DOI: 10.1186/1423-0127-18-45
ISSN: 1423-0127
Subjects: Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000) > BIOCHEMISTRY AND CELL BIOLOGY (060100) > Cellular Interactions (incl. Adhesion Matrix Cell Wall) (060106)
Divisions: Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2011 BioMed Central
Deposited On: 19 Dec 2012 06:52
Last Modified: 13 Jan 2013 15:20

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