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

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

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Department of Gastrointestinal Oncology and Digestive Diseases, The University of Texas M.D. Anderson Cancer Center, Houston 77030. USA.


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.

[Indexed for MEDLINE]

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