Abstract
Abstract PI3K/Akt and MAPk signal transduction pathways are frequently dysregulated in human cancers. Previous work described the molecular basis of pro-survival signals mediated by Akt and MAPk. Mutation in and alteration of these pathways lead to tumorigenesis. However, signal propagation varies across cell type and precise signaling kinetics is less well characterized. The goal of this study is to profile the functional state of the PI3k/Akt and MAPk signaling circuits by coupling cell viability to antibody microarray and immunofluorescence. Simultaneous detection of Akt and MAPk signaling nodes can characterize signaling parameters that correlate to localization patterns across cell type and drug treatment conditions. To examine how signal propagation varied between cell lines, staurosporine was utilized to broadly inhibit protein kinase activity in a cervical cancer cell line, HeLa, and an osteosarcoma cell line, U2-OS, as model systems. To investigate signaling pathways, each cell line was treated and analyzed in parallel by forward phase phospho-specific antibody microarray panels and high content analysis of immunofluorescent staining. Staurosporine inhibited cell proliferation in a time and concentration dependent manner in both cell lines. U2-OS cells had a higher IC50 compared to HeLa cells indicating markedly different signaling parameters between the two models. Our observations suggest detecting cell type specific signaling kinetics can be used as a framework to predict cell sensitivity to specific inhibitors and be used to monitor drug resistance. Note: This abstract was not presented at the meeting. Citation Format: Andrew R. Wagner, Megan Newby, Kary Oakleaf. Multiplex parallel perturbation of Akt and MAPk signaling cascades [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4312.
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