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Ischemia in tumors induces early and sustained phosphorylation changes in stress kinase pathways but does not affect global protein levels

Item Type:Article
Title:Ischemia in tumors induces early and sustained phosphorylation changes in stress kinase pathways but does not affect global protein levels
Creators Name:Mertins, P. and Yang, F. and Liu, T. and Mani, D.R. and Petyuk, V.A. and Gillette, M.A. and Clauser, K.R. and Qiao, J.W. and Gritsenko, M.A. and Moore, R.J. and Levine, D.A. and Townsend, R. and Erdmann-Gilmore, P. and Snider, J.E. and Davies, S.R. and Ruggles, K.V. and Fenyo, D. and Kitchens, R.T. and Li, S. and Olvera, N. and Dao, F. and Rodriguez, H. and Chan, D.W. and Liebler, D. and White, F. and Rodland, K.D. and Mills, G.B. and Smith, R.D. and Paulovich, A.G. and Ellis, M. and Carr, S.A.
Abstract:Protein abundance and phosphorylation convey important information about pathway activity and molecular pathophysiology in diseases including cancer, providing biological insight, informing drug and diagnostic development, and guiding therapeutic intervention. Analyzed tissues are usually collected without tight regulation or documentation of ischemic time. To evaluate the impact of ischemia, we collected human ovarian tumor and breast cancer xenograft tissue without vascular interruption and performed quantitative proteomics and phosphoproteomics after defined ischemic intervals. Although the global expressed proteome and most of the >25,000 quantified phosphosites were unchanged after 60 min, rapid phosphorylation changes were observed in up to 24% of the phosphoproteome, representing activation of critical cancer pathways related to stress response, transcriptional regulation, and cell death. Both pan-tumor and tissue-specific changes were observed. The demonstrated impact of pre-analytical tissue ischemia on tumor biology mandates caution in interpreting stress-pathway activation in such samples and motivates reexamination of collection protocols for phosphoprotein analysis.
Keywords:Breast Neoplasms, Cold Ischemia, Gene Expression Profiling, Heterologous Transplantation, Inbred NOD Mice, Neoplasm Transplantation, Ovarian Neoplasms, Phosphoproteins, Phosphorylation, Proteome, Proteomics, Animals, Mice
Source:Molecular & Cellular Proteomics
Publisher:American Society for Biochemistry and Molecular Biology
Page Range:1690-1704
Date:1 July 2014
Official Publication:https://doi.org/10.1074/mcp.M113.036392
PubMed:View item in PubMed

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