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

Author:
  • Tobias Löfstedt
  • Erik Fredlund
  • Rosa Noguera
  • Samuel Navarro
  • Linda Holmquist Mengelbier
  • Siv Beckman
  • Sven Påhlman
  • Håkan Axelson
Publishing year: 2009
Language: English
Pages: 1924-1936
Publication/Series: Experimental Cell Research
Volume: 315
Issue: 11
Document type: Journal article
Publisher: Academic Press

Abstract english

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.

Keywords

  • Cancer and Oncology

Other

Published
  • CREATE Health
  • ISSN: 1090-2422
Håkan Axelson
E-mail: hakan.axelson [at] med.lu.se

Professor

Division of Translational Cancer Research

+46 46 222 64 34

MV 404 A31A2

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