Src activation of Stat3 is an independent requirement from NF-κB activation for constitutive IL-8 expression in human pancreatic adenocarcinoma cells

Academic Article


  • Human pancreatic tumors often overexpress the angiogenesis-promoting factor Interleukin 8 (IL-8), in part due to overexpression of NF-κB, a frequent occurrence in pancreatic adenocarcinoma. In this study, we demonstrate that reducing c-Src kinase activity, through either pharmacologic inhibition or small interfering RNA-targeted reduction of Src expression, significantly decreased IL-8 expression (P < 0.05) without affecting NF-κB-mediated transcription, but by decreasing phosphorylation of STAT3. To ascertain whether Src-mediated expression of IL-8 was dependent on STAT3, we used stable clones expressing a dominant-negative isoform of STAT3 that inhibits endogenous STAT3 phosphorylation and subsequent DNA binding and STAT3-mediated gene expression or a constitutively activated isoform of STAT3. IL-8 expression was significantly lower in clones expressing the dominant-negative isoform and significantly increased in clones expressing the activated isoform (P < 0.05 for both). Pharmacologic inhibition of NF-κB activity significantly reduced basal IL-8 expression and tumor necrosis factor-induced IL-8 expression (P < 0.05 for both), yet NF-κB activity was not dependent on Src. We therefore suggest that Src activation, through phosphorylation of STAT3, and NF-κB are all required for expression of IL-8 a critical angiogenic-promoting factor in pancreatic adenocarcinomas. © Springer Science+Business Media B.V. 2006.
  • Authors

    Published In

  • Angiogenesis  Journal
  • Digital Object Identifier (doi)

    Author List

  • Trevino JG; Gray MJ; Nawrocki ST; Summy JM; Lesslie DP; Evans DB; Sawyer TK; Shakespeare WC; Watowich SS; Chiao PJ
  • Start Page

  • 101
  • End Page

  • 110
  • Volume

  • 9
  • Issue

  • 2