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Exp Cell Res. 2009 Jul 1;315(11):1924-36. doi: 10.1016/j.yexcr.2009.02.015. Epub 2009 Feb 27.

HIF-1alpha induces MXI1 by alternate promoter usage in human neuroblastoma cells.

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  • 1Center for Molecular Pathology, Department of Laboratory Medicine, Lund University, University Hospital MAS, Entrance 78, S-20502 Malmö, Sweden.


Adaptation to low oxygen conditions is essential for maintaining homeostasis and viability in oxygen-consuming multi-cellular tissues, including solid tumors. Central in these processes are the hypoxia-inducible transcription factors, HIF-1 and HIF-2, controlling genes involved in e.g. glucose metabolism and neovascularization. Tumor hypoxia and HIF expression have also been associated with a dedifferentiated phenotype and increased aggressiveness. In this report we show that the MAX interactor-1 (MXI1) gene is directly regulated by HIF proteins in neuroblastoma and breast cancer cells. HIF-binding and transactivation were detected within MXI1 gene regulatory sequences in the vicinity of the MXI1-0 promoter, leading to rapid induction of the alternate MXI1-0 isoform followed by a long-term induction of both the MXI1-0 and MXI1 isoforms. Importantly, knock-down of MXI1 had limited effect on MYC/MYCN activity under hypoxia, an observation that might be related to the different functional attributes of the two MXI1 isoforms.

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