Network analysis. Ingenuity Pathways analysis (IPA) was used to generate the network overlaid with relative gene expression levels measured in directly irradiated cells at 30 minutes (a) and 4 hours (b). The network was built by selecting genes encoding inter-cellular signals responding early to radiation that could lead to activation of Akt. We hypothesized that Akt activation followed by post-translation modification of GSK3β and β-catenin would have an effect on gene expression. FAS, DKK1 and LAMC2 were induced at 4 hours but not at 30 minutes. MMP3 (figure 2a, heatmap) and MT1L were induced at 30 minutes as well as 4 hours. The dynamics of Akt signaling at the protein level in the 30-minute to 4-hour time interval are further investigated in Figure 4. Nodes representing gene products are displayed by cellular localization (extracellular space, plasma membrane, cytoplasm or nucleus). Node color indicates up-regulated genes (red) and down-regulated genes (green); scale bar indicates the range of expression ratios. Edges (lines and arrows between nodes) represent direct (solid lines) and indirect (dashed lines) interactions between molecules as supported by information in the Ingenuity knowledge base. We indicate Akt, GSK3β and β-catenin (CTNNB1) and their relationship edges in blue to highlight the signaling axis focused on in the following figure 4. Node shapes represent functional classes of gene products; rectangles with solid lines for cytokines, rectangles with dotted lines for growth factors, triangles for phosphatases, concentric circles for groups or complexes, diamonds for enzymes, and ovals for transcriptional regulators or modulators.
Ghandhi et al. BMC Medical Genomics 2010 3:31 doi:10.1186/1755-8794-3-31