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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Shi, Q; Le, X; Abbruzzese, JL; Wang, B; Mujaida, N; Matsushima, K; Huang, S; Xiong, Q; Xie, K

Published Date

  • December 1999

Published In

Volume / Issue

  • 19 / 12

Start / End Page

  • 1363 - 1371

PubMed ID

  • 10638705

Pubmed Central ID

  • 10638705

Electronic International Standard Serial Number (EISSN)

  • 1557-7465

International Standard Serial Number (ISSN)

  • 1079-9907

Digital Object Identifier (DOI)

  • 10.1089/107999099312821

Language

  • eng