Linked Life Data

18454179

Source:http://linkedlifedata.com/resource/pubmed/id/18454179

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
34
pubmed:dateCreated
2008-8-7
pubmed:abstractText
Reactive oxygen species (ROS)-generating enzyme Nox1 is important in the induction of oncogenic Ras transformation phenotypes, but it is not defined whether Nox1 is involved in Ras-induced upregulation of vascular endothelial growth factor (VEGF), a potent stimulator of tumor angiogenesis. Here we describe that ablation of the Nox1 activity by Nox1 small-interference RNAs (siRNAs) or diphenylene iodonium (DPI) inhibited synthesis of both VEGF proteins and VEGF mRNAs in K-Ras transformed normal rat kidney (KNRK) cells. Nox1siRNAs and DPI suppressed extracellular signal-regulated kinase (ERK)-dependent phosphorylation of a transcription factor Sp1 and Sp1 binding to a VEGF promoter. Furthermore, tumors derived from Nox1siRNA-transfected KNRK cells markedly decreased neovascularization. The Nox1 activity was required for VEGF production in human colon cancer CaCO-2 cells, as in the case of KNRK cells. However, since overexpression of Nox1 in normal rat kidney cells failed to induce VEGF, the Nox1 activity alone was not sufficient to upregulate VEGF expression, which suggests that unlike the previously proposed model, Nox1 may act in concert with other effectors integrated into the Ras network. We propose that Nox1 mediates oncogenic Ras-induced upregulation of VEGF and angiogenesis by activating Sp1 through Ras-ERK-dependent phosphorylation of Sp1.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1476-5594
pubmed:author
pubmed:issnType
Electronic
pubmed:day
7
pubmed:volume
27
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4724-32
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
NADPH oxidase 1 plays a critical mediating role in oncogenic Ras-induced vascular endothelial growth factor expression.
pubmed:affiliation
Department of Molecular Biology and Biochemistry, Shinshu University Graduate School of Medicine, Matsumoto, Nagano, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't