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Stem cell factor induces HIF-1alpha at normoxia in hematopoietic cells.

Pedersen, Malin LU ; Löfstedt, Tobias LU ; Sun, Jianmin LU ; Holmquist Mengelbier, Linda LU ; Påhlman, Sven LU and Rönnstrand, Lars LU (2008) In Biochemical and Biophysical Research Communications 98(103). p.98-103
Abstract
Signaling by the receptor for stem cell factor (SCF), c-Kit, is of major importance for hematopoiesis, melanogenesis and reproduction, and the biological responses are commonly proliferation and cell survival. Thus, constitutive activation due to c-Kit mutations is involved in the pathogenesis of several forms of cancer, e.g. leukemias, gastrointestinal stromal tumors and testicular tumors. Tumor survival requires oxygen supply through induced neovascularization, a process largely mediated by the vascular endothelial growth factor (VEGF), a prominent target of the transcription factors hypoxia-inducible factor-1 (HIF-1) and HIF-2. Using Affymetrix microarrays we have identified genes that are upregulated following SCF stimulation.... (More)
Signaling by the receptor for stem cell factor (SCF), c-Kit, is of major importance for hematopoiesis, melanogenesis and reproduction, and the biological responses are commonly proliferation and cell survival. Thus, constitutive activation due to c-Kit mutations is involved in the pathogenesis of several forms of cancer, e.g. leukemias, gastrointestinal stromal tumors and testicular tumors. Tumor survival requires oxygen supply through induced neovascularization, a process largely mediated by the vascular endothelial growth factor (VEGF), a prominent target of the transcription factors hypoxia-inducible factor-1 (HIF-1) and HIF-2. Using Affymetrix microarrays we have identified genes that are upregulated following SCF stimulation. Interestingly, many of the genes induced were found to be related to a hypoxic response. These findings were corroborated by our observation that SCF stimulation of the hematopoietic cell lines M-07e induces HIF-1alpha and HIF-2alpha protein accumulation at normoxia. In addition, SCF-induced HIF-1alpha was transcriptionally active, and transcribed HIF-1 target genes such as VEGF, BNIP3, GLUT1 and DEC1, an effect that could be reversed by siRNA against HIF-1alpha. We also show that SCF-induced accumulation of HIF-1alpha is dependent on both the PI-3-kinase and Ras/MEK/Erk pathways. Our data suggest a novel mechanism of SCF/c-Kit signaling in angiogenesis and tumor progression. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Receptor, tyrosine kinase, Hypoxia, HIF-1 alpha, Affymetrix, Stem cell factor, c-Kit
in
Biochemical and Biophysical Research Communications
volume
98
issue
103
pages
98 - 103
publisher
Elsevier
external identifiers
  • wos:000260738500019
  • pmid:18834862
  • scopus:54449090771
ISSN
1090-2104
DOI
10.1016/j.bbrc.2008.09.102
language
English
LU publication?
yes
id
8fbfeb13-6cb2-495d-9714-1b415aceaefc (old id 1262577)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/18834862?dopt=Abstract
date added to LUP
2008-11-10 15:55:50
date last changed
2017-11-19 03:46:49
@article{8fbfeb13-6cb2-495d-9714-1b415aceaefc,
  abstract     = {Signaling by the receptor for stem cell factor (SCF), c-Kit, is of major importance for hematopoiesis, melanogenesis and reproduction, and the biological responses are commonly proliferation and cell survival. Thus, constitutive activation due to c-Kit mutations is involved in the pathogenesis of several forms of cancer, e.g. leukemias, gastrointestinal stromal tumors and testicular tumors. Tumor survival requires oxygen supply through induced neovascularization, a process largely mediated by the vascular endothelial growth factor (VEGF), a prominent target of the transcription factors hypoxia-inducible factor-1 (HIF-1) and HIF-2. Using Affymetrix microarrays we have identified genes that are upregulated following SCF stimulation. Interestingly, many of the genes induced were found to be related to a hypoxic response. These findings were corroborated by our observation that SCF stimulation of the hematopoietic cell lines M-07e induces HIF-1alpha and HIF-2alpha protein accumulation at normoxia. In addition, SCF-induced HIF-1alpha was transcriptionally active, and transcribed HIF-1 target genes such as VEGF, BNIP3, GLUT1 and DEC1, an effect that could be reversed by siRNA against HIF-1alpha. We also show that SCF-induced accumulation of HIF-1alpha is dependent on both the PI-3-kinase and Ras/MEK/Erk pathways. Our data suggest a novel mechanism of SCF/c-Kit signaling in angiogenesis and tumor progression.},
  author       = {Pedersen, Malin and Löfstedt, Tobias and Sun, Jianmin and Holmquist Mengelbier, Linda and Påhlman, Sven and Rönnstrand, Lars},
  issn         = {1090-2104},
  keyword      = {Receptor,tyrosine kinase,Hypoxia,HIF-1 alpha,Affymetrix,Stem cell factor,c-Kit},
  language     = {eng},
  number       = {103},
  pages        = {98--103},
  publisher    = {Elsevier},
  series       = {Biochemical and Biophysical Research Communications},
  title        = {Stem cell factor induces HIF-1alpha at normoxia in hematopoietic cells.},
  url          = {http://dx.doi.org/10.1016/j.bbrc.2008.09.102},
  volume       = {98},
  year         = {2008},
}