PMID- 18834862
OWN - NLM
STAT- MEDLINE
DCOM- 20081128
LR  - 20201214
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 377
IP  - 1
DP  - 2008 Dec 5
TI  - Stem cell factor induces HIF-1alpha at normoxia in hematopoietic cells.
PG  - 98-103
LID - 10.1016/j.bbrc.2008.09.102 [doi]
AB  - 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.
FAU - Pedersen, Malin
AU  - Pedersen M
AD  - Department of Laboratory Medicine, Lund University, Malmo University Hospital, 
      Malmo, Sweden.
FAU - Lofstedt, Tobias
AU  - Lofstedt T
FAU - Sun, Jianmin
AU  - Sun J
FAU - Holmquist-Mengelbier, Linda
AU  - Holmquist-Mengelbier L
FAU - Pahlman, Sven
AU  - Pahlman S
FAU - Ronnstrand, Lars
AU  - Ronnstrand L
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20081001
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (BNIP3 protein, human)
RN  - 0 (DELEC1 protein, human)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Membrane Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Stem Cell Factor)
RN  - 0 (Tumor Suppressor Proteins)
RN  - 0 (VEGFA protein, human)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 2.7.11.25 (MAP Kinase Kinase Kinases)
RN  - EC 3.6.5.2 (ras Proteins)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Animals
MH  - Cell Hypoxia
MH  - Cell Line, Tumor
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Gene Expression Regulation, Leukemic
MH  - Hematopoietic Stem Cells/drug effects/*metabolism
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism
MH  - MAP Kinase Kinase Kinases/metabolism
MH  - Membrane Proteins/genetics
MH  - Mice
MH  - Neoplasms/blood supply/pathology
MH  - Neovascularization, Pathologic/genetics/metabolism
MH  - Neovascularization, Physiologic
MH  - Oxygen/metabolism
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Proto-Oncogene Proteins/genetics
MH  - Stem Cell Factor/genetics/pharmacology/*physiology
MH  - Transfection
MH  - Tumor Suppressor Proteins/genetics
MH  - Vascular Endothelial Growth Factor A/genetics
MH  - ras Proteins/metabolism
EDAT- 2008/10/07 09:00
MHDA- 2008/12/17 09:00
CRDT- 2008/10/07 09:00
PHST- 2008/09/19 00:00 [received]
PHST- 2008/09/20 00:00 [accepted]
PHST- 2008/10/07 09:00 [pubmed]
PHST- 2008/12/17 09:00 [medline]
PHST- 2008/10/07 09:00 [entrez]
AID - S0006-291X(08)01857-3 [pii]
AID - 10.1016/j.bbrc.2008.09.102 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2008 Dec 5;377(1):98-103. doi: 
      10.1016/j.bbrc.2008.09.102. Epub 2008 Oct 1.