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A proteomics analysis of cell signaling alterations in colorectal cancer.

Abstract
To gain further insight into alterations in cellular pathways, tumor profiling, and marker discovery in colorectal cancer (CRC) we used a new antibody microarray specific for cell signaling. Soluble protein extracts were prepared from paired tumor/normal biopsies of 11 patients diagnosed with colorectal carcinoma at different stages; four liver carcinomas were used as a reference. Antibody microarray analysis identified 46 proteins that were differentially expressed between normal colorectal epithelium and adenocarcinoma. These proteins gave a specific signature for CRC, different from other tumors, as well as a panel of novel markers and potential targets for CRC. Twenty-four proteins were validated by using a specific colorectal cancer tissue microarray and immunoblotting analysis. Together with some previously well known deregulated proteins in CRC (beta-catenin, c-MYC, or p63), we found new potential markers preferentially expressed in CRC tumors: cytokeratin 13, calcineurin, CHK1, clathrin light chain, MAPK3, phospho-PTK2/focal adhesion kinase (Ser-910), and MDM2. CHK1 antibodies were particularly effective in discriminating between tumoral and normal mucosa in CRC. Moreover a global picture of alterations in signaling pathways in CRC was observed, including a significant up-regulation of different components of the epidermal growth factor receptor and Wnt/beta-catenin pathways and the down-regulation of p14(ARF). The experimental approach described here should be applicable to other pathologies and neoplastic processes.
AuthorsJuan Madoz-Gúrpide, Marta Cañamero, Lydia Sanchez, José Solano, Patricia Alfonso, J Ignacio Casal
JournalMolecular & cellular proteomics : MCP (Mol Cell Proteomics) Vol. 6 Issue 12 Pg. 2150-64 (Dec 2007) ISSN: 1535-9476 [Print] United States
PMID17848589 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Neoplasm Proteins
Topics
  • Adult
  • Aged
  • Aged, 80 and over
  • Colorectal Neoplasms (metabolism)
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Neoplasm Proteins (metabolism)
  • Proteomics
  • Signal Transduction

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