Proteomics in studies of signal transduction in epithelial cells.

An understanding of the complexity of cancer is important for correct diagnostics and efficient treatment of this disease. Recent developments of proteomics technologies allow us to address the complexity of tumorigenesis at a level of global protein profiling. This review discusses recent studies of signaling processes in cells of epithelial origin undertaken with the use of global protein profiling. Tumors of epithelial origin comprise about 90% of human breast cancers, and it is believed that transformation of breast epithelial cells shares common features of transformation with other mammalian cells: destabilization of the genome followed by acquisition of immortalization, unrestricted growth, evasion of death-inducing signals, and acquisition of invasive and tumor promoting characteristics. Functional proteomics of growth-promoting, growth-inhibiting, and pro-apoptotic signaling pathways, in combination with proteomics studies of breast epithelial cell differentiation and profiling of breast tumorigenesis, revealed groups of regulated proteins: structural components, stress-regulated proteins, regulators of transcription, translation and RNA processing, and regulators of posttranslational modifications, e.g., kinases, phosphatases, and proteases. The first lesson of proteomics studies is the discovery of significant number of new targets, as compared to total number of affected proteins. The second lesson is the poor correlation between expressions of proteins and their mRNAs. The third lesson is the low amplitude of protein changes compared to that observed for mRNA. These observations also recommend the analysis of signaling patterns rather than separate signaling pathways.