FIGURE 1.

Phosphatidylinositol 3-kinase is a central hub in signaling pathways required for estrogen-independent ER+ breast cancer cell growth. MCF-7/LTED cells transiently transfected with a siRNA library targeting 779 kinases were reseeded in hormone-depleted medium. Cell viability was measured 4–5 days later by Alamar blue assay. Median cell growth in four independent experiments was calculated for each kinase siRNA relative to non-silencing controls. Individual knockdown of 42 kinases inhibited MCF-7/LTED cell growth ≥33% (p ≤ 0.05) in at least three of four experiments (detailed in Fox et al., 2011). Ingenuity Pathways Analysis revealed that these 42 kinases map to several protein networks that overlap with PI3K signaling (red box, enlarged in bottom panel). Proteins involved in these networks are displayed as nodes. Solid lines indicate direct relationships between proteins, and dotted lines indicate indirect interactions. Green nodes represent the kinases identified in the screen, as well as others whose knockdown was predicted by the Ingenuity software to negatively affect cell growth. The various nodal shapes represent the functional class of the gene product.