Insights into erlotinib action in pancreatic cancer cells using a combined experimental and mathematical approach

Figure 1 Flow chart of epidermal growth factor signal transduction and the ordinary differential equation network. A: Simplified reaction network. Solid black arrows show epidermal growth factor-dependent processes, whereas grey arrows represent basal phosphorylation. Two epidermal growth factor receptor (EGFR)-dependent negative feedback loops are shown by black dotted lines; B: Translation of the reaction network into an ordinary differential equation (ODE) model describing EGFR-mediated signal transduction; C: Ratio of basal levels of phosphorylated protein kinase B (AKT) (r_pA) and extracellular signal-regulated kinase (ERK) (r_pE) in BxPC-3 (superscript B) and Capan-1 (superscript C) cells. These calculations are implemented in the mathematical model; D: Equations describe relations between observables (fitted to experimental data) and model variables. For further description see “mathematical model” in the “materials and methods” section. EGF: Epidermal growth factor; pAKT: Phospho-AKT; ERK: Extracellular signal-regulated kinase; pERK: Phospho-ERK; WB: Western blot.