Systems-based analysis of responses to stimulation or inhibition of EGF receptor signaling in breast cancer cells

摘要: 4427 Comprehensive assessment of molecular and cellular responses to stimulation or inhibition the EGFR pathway is a prerequisite for generation optimization computerized models this pathway. Pathway Logic rule-based model that uses rewrite logic symbolically represent biological processes. To expand rule set model, we performed an extensive temporal analysis EGF MEK in two breast cancer cell lines (T47D MBA-MD-231). RNA expression array analyses reverse-phase protein lysate were performed. In addition, changes cycle distribution, viability, apoptosis rates measured. Unsupervised cluster was canonical-pathway based system GenMAPP used map observed onto known pathways. Expected clearly reproduced, including early-growth response includes activation transcription factors c-Jun/c-Fos dual-specificity phosphatases, which are be negative regulators Ras-MEK-ERK signaling. evidence crosstalk feedback loops found. For example, increased receptor possible transcripition down-stream PI3-kinase following Since time-course experiment also suggestive cross-talk between signaling as well TGF-beta pathway, currently testing role these pathways mediators therapeutic resistance inhibition. Data from being thus allowing better prediction targeted interventions into signal transduction