Abstract
Pancreatic cancer is the fourth leading cause of cancer-related deaths in the United States. Based on genomic studies, a number of genes that have somatic mutations including CDKN2A, SMAD4, TP53 and KRAS have been identified in pancreatic cancers. Recently, a comprehensive genomic analysis was performed in a panel of 14 primary pancreatic cancer cell lines and 10 xenografts, in which ∼1,500 somatic alterations were identified and a core set of 12 signaling pathways were defined.
In this study, we characterized the 14 primary pancreatic cancer cell lines whose genomes have been sequenced. From Western blots using anti-phosphotyrosine antibodies, we observed a heterogeneous pattern of tyrosine phosphorylation in these cell lines, indicating that different tyrosine kinases were likely activated in different cells. Phosphotyrosine-containing peptides were enriched by immunoprecipitation by anti-phosphotyrosine antibodies. The enriched phosphopeptides were analyzed on a high resolution Fourier transform mass spectrometer coupled to nanoflow reverse phase liquid chromatography.
Our preliminary data indicates that the approach used in this study is suitable for the global profiling of tyrosine kinase pathways that are abnormally activated in pancreatic cancers. For example, lymphocyte-specific protein tyrosine kinase and spleen tyrosine kinase were observed to be activated in one of pancreatic cancer cell lines (Panc 8.13), while insulin receptor was activated in different cell lines (Panc 198).
Citation Information: Cancer Prev Res 2010;3(12 Suppl):A58.
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