Figure 3. Network analysis of genes under-expressed in MCF-7/MET-R cells that have acquired resistance to metformin. A data set containing the differentially downregulated genes (called the focus molecules = 366) between metformin-refractory MCF-7/MET-R cells and metformin-sensitive MCF-7 parental cells was overlaid onto a global molecular network developed from information contained in the Ingenuity Pathway (IPA) Knowledge Base. Networks of these focus molecules were then algorithmically generated based on their connectivity. The figure shows downregulated networks with the 5 highest IPA scores (a composite measure that indicates the statistically significance of the interconnection between the molecules depicted in the network). The focus molecules are colored according to the gene expression (fold-change). The nodes are displayed using various shapes that represent the functional class of the gene product. Edges with dashed lines indicate indirect interactions, while continuous lines represent direct interactions.