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

Chambers KF, Pearson JF, Pellacani D, Aziz N, Gužvić M, Klein CA, Lang SH - J. Biomed. Sci. (2011)

Bottom Line: 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).We show that this morphological effect is associated with gene expression changes to TGF beta signalling, cytoskeleton and anion activity.

View Article: PubMed Central - HTML - PubMed

Affiliation: Yorkshire Cancer Research Unit, Dept, Biology, University of York, Heslington, York YO10 5YW, UK.

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.

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Related in: MedlinePlus

Genes identified in the TGF beta pathway. The Kegg pathway for TGF beta signalling illustrating the significant genes identified by pathway express. Genes circled in red indicate genes indicate genes from the primary cell microarray dataset (Operon) and those in blue from the BPH-1 cell microarray dataset (Affymetrix). Continuous lines are upregulated genes whereas broken lines are down-regulated.
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Figure 3: Genes identified in the TGF beta pathway. The Kegg pathway for TGF beta signalling illustrating the significant genes identified by pathway express. Genes circled in red indicate genes indicate genes from the primary cell microarray dataset (Operon) and those in blue from the BPH-1 cell microarray dataset (Affymetrix). Continuous lines are upregulated genes whereas broken lines are down-regulated.

Mentions: Figure 3 shows the Kyoto Encyclopedia of Genes and Genomes (Kegg) pathway for TGF beta signalling [15-17] and illustrates the significant genes found by Pathway Express for both primary and cell line microarray datasets. No gene was expressed by both arrays on the Kegg pathway. The primary cultures showed upregulation of ACVR1B (activin receptor type-1B) and DCN (decorin) and down regulation of SARA (ZFYVE9) in response to stromal co-culture. BPH-1 cells showed upregulation of INHBB (inhibin beta chain) and down regulation of FST (follistatin), MYC, THBS1 (thrombospondin 1) and ID1.


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

Chambers KF, Pearson JF, Pellacani D, Aziz N, Gužvić M, Klein CA, Lang SH - J. Biomed. Sci. (2011)

Genes identified in the TGF beta pathway. The Kegg pathway for TGF beta signalling illustrating the significant genes identified by pathway express. Genes circled in red indicate genes indicate genes from the primary cell microarray dataset (Operon) and those in blue from the BPH-1 cell microarray dataset (Affymetrix). Continuous lines are upregulated genes whereas broken lines are down-regulated.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3141633&req=5

Figure 3: Genes identified in the TGF beta pathway. The Kegg pathway for TGF beta signalling illustrating the significant genes identified by pathway express. Genes circled in red indicate genes indicate genes from the primary cell microarray dataset (Operon) and those in blue from the BPH-1 cell microarray dataset (Affymetrix). Continuous lines are upregulated genes whereas broken lines are down-regulated.
Mentions: Figure 3 shows the Kyoto Encyclopedia of Genes and Genomes (Kegg) pathway for TGF beta signalling [15-17] and illustrates the significant genes found by Pathway Express for both primary and cell line microarray datasets. No gene was expressed by both arrays on the Kegg pathway. The primary cultures showed upregulation of ACVR1B (activin receptor type-1B) and DCN (decorin) and down regulation of SARA (ZFYVE9) in response to stromal co-culture. BPH-1 cells showed upregulation of INHBB (inhibin beta chain) and down regulation of FST (follistatin), MYC, THBS1 (thrombospondin 1) and ID1.

Bottom Line: 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).We show that this morphological effect is associated with gene expression changes to TGF beta signalling, cytoskeleton and anion activity.

View Article: PubMed Central - HTML - PubMed

Affiliation: Yorkshire Cancer Research Unit, Dept, Biology, University of York, Heslington, York YO10 5YW, UK.

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.

Show MeSH
Related in: MedlinePlus