Cooperation between transcription factor AP-1 and NF-kappaB in the induction of interleukin-8 in human pancreatic adenocarcinoma cells by hypoxia

J Interferon Cytokine Res. 1999 Dec;19(12):1363-71. doi: 10.1089/107999099312821.


The expression of interleukin-8 (IL-8) has been shown to play an important role in the growth and metastasis of human pancreatic cancer. In the present study, we investigated the regulation of IL-8 gene expression by hypoxic environments. Exposure of the human pancreatic cancer cells COLO357 and FG to hypoxia in culture resulted in a time-dependent increase in steady-state levels of IL-8 mRNA and IL-8 protein secretion. The induction of IL-8 expression was correlated with transcriptional activation of the IL-8 gene. Deletion and point mutation analyses of the IL-8 promoter revealed that both AP-1 and NF-kappaB binding sites were necessary for IL-8 induction by hypoxia. Consistently, hypoxia induced both AP-1 and NF-kappaB activity. These data suggest that hypoxic environments upregulate the IL-8 gene via cooperation of NF-kappaB and AP-1 and contribute to the progression and metastasis of human pancreatic cancer.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / immunology
  • Adenocarcinoma / metabolism
  • Base Sequence
  • Cell Hypoxia / genetics*
  • Cell Hypoxia / physiology*
  • DNA Primers / genetics
  • Humans
  • Interleukin-8 / biosynthesis*
  • Interleukin-8 / genetics*
  • NF-kappa B / metabolism*
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / immunology
  • Pancreatic Neoplasms / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism
  • Transcription Factor AP-1 / metabolism*
  • Transcriptional Activation
  • Up-Regulation


  • DNA Primers
  • Interleukin-8
  • NF-kappa B
  • RNA, Messenger
  • RNA, Neoplasm
  • Transcription Factor AP-1