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:
https://lup.lub.lu.se/record/1262577
- author
- Pedersen, Malin
LU
; Löfstedt, Tobias
LU
; Sun, Jianmin
LU
; Holmquist Mengelbier, Linda
LU
; Påhlman, Sven
LU
and Rönnstrand, Lars
LU
- organization
- publishing date
- 2008
- 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
- pmid:18834862
- 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
- 2016-04-01 13:31:25
- date last changed
- 2022-04-21 22:03:47
@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}},
keywords = {{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}},
doi = {{10.1016/j.bbrc.2008.09.102}},
volume = {{98}},
year = {{2008}},
}