Stat3 activation regulates the expression of vascular endothelial growth factor and human pancreatic cancer angiogenesis and metastasis

摘要: Expression of vascular endothelial growth factor (VEGF), a key angiogenic protein, has been linked with pancreatic cancer progression. However, the molecular basis for VEGF overexpression remains unclear. Immunohistochemical studies have indicated that coincides elevated Stat3 activation in human specimens. In our study, more than 80% cell lines used exhibited constitutively activated Stat3, correlated expression level. Blockade via ectopic dominant-negative significantly suppressed expression, angiogenesis, tumor growth, and metastasis vivo. Furthermore, directly promoter, whereas inhibited promoter. A putative Stat3-responsive element on promoter was identified using protein-DNA binding assay confirmed mutagenesis assay. These results indicate regulates hence cancer, suggesting signaling may be targeted treatment cancer.