Hypoxia-induced secretion of macrophage migration-inhibitory factor from MCF-7 breast cancer cells is regulated in a hypoxia-inducible factor-independent manner.
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 24h but up-regulation of MIF mRNA was minimal. Inhibition of HIF-1alpha, HIF-2alpha, NF-kappaB and C/EBPbeta 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.
Larsen
Mona
M
Laboratory of Experimental Oncology, Institute of Molecular Pathology, University of Copenhagen, Copenhagen, Denmark.
Tazzyman
Simon
S
Lund
Eva L
EL
Junker
Nanna
N
Lewis
Claire E
CE
Kristjansen
Paul E G
PE
Murdoch
Craig
C
D051792:Basic Helix-Loop-Helix Proteins / Q000502:physiology*; D001943:Breast Neoplasms / Q000378:metabolism*; D018929:Cell Culture Techniques / Q000379:methods; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors; D008263:Macrophage Migration-Inhibitory Factors / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D051792:Basic Helix-Loop-Helix Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008263:Macrophage Migration-Inhibitory Factors; D034741:RNA, Small Interfering; D042461:Vascular Endothelial Growth Factor A