1668P - Systems Biology in Translational Oncology: Computational and Experimental Study of EGFR and IGF1R Pathways in NSCLC Cell Lines

Abstract

ABSTRACT Background The epidermal growth factor receptor (EGFR) and type 1 insulin-like growth factor receptor (IGF1R) pathways are complex networks involving interactions between membrane-bound receptors, ligands, binding proteins, downstream effectors and mutual interactions. In this study we have designed a computational model of EGFR and IGF1R pathways in NSCLC and we validated their dynamic responses in several tumor cell lines. Materials and methods EGFR and IGF1R pathways and the downstream MAPK and PIK3 networks have been modeled by means a mathematical model based on ODE. A549, H1299, H1675 and H1650 tumor cell lines were stimulated by EGF, IGF-I, EGF/IGF-I and without ligands. For these induction conditions we quantified at 0, 2, 5, 10, 20, 30, 40, 50, 60 minutes by western blotting the following proteins: phospho-AKT, AKT, phospho-EGFR, EGFR, phospho-p44/42 MAPK(ERK 1/2), p44/42 MAPK(ERK1/2), phospho-IGF1R and IGF1R. Model simulations and experiment data have been combined together. Results The time series performed in all cell lines under the four induction conditions allowed us to characterize the signal transduction through EGFR and IGF1R pathways. Our model has reproduced proteins behavior of A549, H1299, H1675 and H1650 cell lines and also the robustness of the network has been confirmed. Conclusions We propose a Systems Biology approach, combined with Translational Oncology tolls, to understand the interaction between EGFR and IGF1R pathways in NSCLC cell lines and validate model predictions. Future work will investigate the effect of drugs action on cell lines. Disclosure All authors have declared no conflicts of interest.