Immunohistochemical analysis of changes in signaling pathway activation downstream of growth factor receptors in pancreatic duct cell carcinogenesis

摘要: The pathogenesis of pancreatic ductal adenocarcinoma (PDAC) involves multi-stage development molecular aberrations affecting signaling pathways that regulate cancer growth and progression. This study was performed to gain a better understanding the abnormal occurs in PDAC compared with normal duct epithelia. We immunohistochemistry on tissue microarray 26 PDAC, 13 appearing adjacent epithelia, 12 non-PDAC ducts. levels 18 proteins including factor receptors, tumor suppressors their putative downstream phosphorylated (p-) signal transducers those overall profiles protein expression levels, activation states sub-cellular distribution cells were distinguishable from non-neoplastic ERK pathway correlated high S2448p-mTOR (100%, p = 0.05), T389p-S6K 0.02 S235/236p-S6 (86%, 0.005). Additionally, S727p-STAT3 Advanced tumors lymph node metastasis characterized by S276p-NFκB 0.05) S9p-GSK3β 0.05). High PKBβ/AKT2, EGFR, as well nuclear T202/Y204p-ERK T180/Y182p-p38 observed ducts non-cancerous pancreas. Multiple are activated cell carcinogenesis associated ERK, PKB/AKT, mTOR STAT3 pathways. appears also increased epithelia carcinoma, suggesting micro-environmental effects.