Journal
CANCER LETTERS
Volume 265, Issue 2, Pages 239-249Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2008.02.012
Keywords
macrophage migration-inhibitory factor; hypoxia; hypoxia-inducible factor; breast cancer
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Funding
- Biotechnology and Biological Sciences Research Council Funding Source: Medline
- Cancer Research UK Funding Source: Medline
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The cytokine MIF is over-expressed in tumors and is associated with tumor proliferation, angiogenesis and metastasis. Hypoxia, a hallmark feature of tumors, increases MIF expression from tumor cells. We examined the role of hypoxia-inducible transcription factors on MIF secretion from MCF-7 breast carcinoma cells. Secretion of MIF was induced by hypoxia after 24 h but up-regulation of MIF mRNA was minimal. Inhibition of HIF-1 alpha, HIF-2 alpha, NF-kappa B and C/EBP beta using siRNA had no effect on hypoxia-induced MIF secretion. However, inhibition of transcription and translation significantly decreased MIF production, suggesting that hypoxia-induced secretion of MIF in MCF-7 cells is via an alternative pathway. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
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