Candidate genes for the hypoxic tumor phenotype

Albert C. Koong, Nicholas C. Denko, Karen M. Hudson, Cornelia Schindler, Lillian Swiersz, Cameron Koch, Sydney Evans, Hani Ibrahim, Quynh T. Le, David J Terris, Amato J. Giaccia

Research output: Contribution to journalArticle

305 Scopus citations

Abstract

In this study, we have analyzed changes induced by hypoxia at the transcriptional level of genes that could be responsible for a more aggressive phenotype. Using a series of DNA array membranes, we identified a group of hypoxia-induced genes that included plasminogen activator inhibitor- 1 (PAI-1), insulin-like growth factor-binding protein 3 (IGFBP-3), endothelin-2, low-density lipoprotein receptor-related protein (LRP), BCL2- interacting killer (BIK), migration-inhibitory factor (MIF), matrix metalloproteinase-13 (MMP-13), fibroblast growth factor-3 (FGF-3), GADD45, and vascular endothelial growth factor (VEGF). The induction of each gene was confirmed by Northern blot analysis in two different squamous cell carcinoma- derived cell lines. We also analyzed the kinetics of PAI-1 induction by hypoxia in more detail because it is a secreted protein that may serve as a useful molecular marker of hypoxia. On exposure to hypoxia, there was a gradual increase in PAI-1 mRNA between 2 and 24 h of hypoxia followed by a rapid decay after 2 h of reoxygenation. PAI-1 levels were also measured in the serum of a small group of head and neck cancer patients and were found to correlate with the degree of tumor hypoxia found in these patients.

Original languageEnglish (US)
Pages (from-to)883-887
Number of pages5
JournalCancer Research
Volume60
Issue number4
StatePublished - Feb 15 2000
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Koong, A. C., Denko, N. C., Hudson, K. M., Schindler, C., Swiersz, L., Koch, C., Evans, S., Ibrahim, H., Le, Q. T., Terris, D. J., & Giaccia, A. J. (2000). Candidate genes for the hypoxic tumor phenotype. Cancer Research, 60(4), 883-887.