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1 Department of Internal Medicine, University of Florence, Florence, Italy
2 Department of Chemistry, University of Minnesota, Duluth, MN, USA
3 Department of General Surgery, University of Florence, Florence, Italy
4 Department of Molecular Biosciences, University of California, Davis, CA, USA
* To whom correspondence should be addressed. E-mail: cgiulivi{at}ucdavis.edu.
The focus of this study was to use differential protein expression to investigate operative pathways in early stages of human colon cancer. Colorectal cancer represents an ideal model system to study development and progression of human tumors, and the proteomics approach avoids overlooking posttranslational modifications, not detected by microarray analyses, and the limited correlation between transcript and protein levels. Colon cancer samples, confined to the intestinal wall, were analyzed by expression proteomics and compared to matched samples from normal colon tissue. Samples were processed by 2DGE and, spots differentially expressed and consistent across all patients, were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-ToF-MS) analyses and by western blotting. After analyzing differentially expressed proteins and their metabolic pathways, the following main conclusions were achieved for the tumor tissue: a) a shift from beta-oxidation, as the main source of energy, to anaerobic glycolysis was observed owed to the alteration of nuclear- vs. mitochondrial-encoded proteins and other proteins related to fatty acid and carbohydrate metabolism; b) lower capacity for Na+ and K+ cycling; c) operativity of the apoptosis pathway, especially the mitochondrial one. This study of the human colon cancer proteome represents a step towards a better understanding of the metabolomics of colon cancer at early stages, confined to the intestinal wall.
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