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

Löfstedt, Tobias LU ; Fredlund, Erik LU ; Noguera, Rosa; Navarro, Samuel; Holmquist Mengelbier, Linda LU ; Beckman, Siv LU ; Påhlman, Sven LU and Axelson, Håkan LU (2009) In Experimental Cell Research 315(11). p.1924-1936
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Experimental Cell Research
volume
315
issue
11
pages
1924 - 1936
publisher
Academic Press
external identifiers
  • wos:000266656000014
  • pmid:19254710
  • scopus:67049137354
ISSN
1090-2422
DOI
10.1016/j.yexcr.2009.02.015
project
CREATE Health
language
English
LU publication?
yes
id
cb53378f-2281-4104-b20e-30d1477a5aea (old id 1368096)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19254710?dopt=Abstract
date added to LUP
2009-04-03 12:23:01
date last changed
2017-08-06 03:44:13
@article{cb53378f-2281-4104-b20e-30d1477a5aea,
  abstract     = {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.},
  author       = {Löfstedt, Tobias and Fredlund, Erik and Noguera, Rosa and Navarro, Samuel and Holmquist Mengelbier, Linda and Beckman, Siv and Påhlman, Sven and Axelson, Håkan},
  issn         = {1090-2422},
  language     = {eng},
  number       = {11},
  pages        = {1924--1936},
  publisher    = {Academic Press},
  series       = {Experimental Cell Research},
  title        = {HIF-1alpha induces MXI1 by alternate promoter usage in human neuroblastoma cells.},
  url          = {http://dx.doi.org/10.1016/j.yexcr.2009.02.015},
  volume       = {315},
  year         = {2009},
}