Linked Life Data

15172974

Source:http://linkedlifedata.com/resource/pubmed/id/15172974

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2004-6-2
pubmed:abstractText
The activation of the microvascular endothelial cell platelet-derived growth factor (PDGF) receptor (PDGF-R) by PDGF has been implicated in neoplastic angiogenesis. Here, we established cultures of murine bone microvascular endothelial cells and examined their response to stimulation with PDGF BB ligand and to blockade of PDGF-R signaling with the tyrosine kinase inhibitor STI571 (Gleevec). The addition of STI571 to cultures of bone endothelial cells blocked PDGF BB-induced phosphorylation in a dose-dependent manner and completely abrogated the activation of downstream targets Akt and ERK1/2. Coadministration of STI571 and Taxol also induced the activation of procaspase-3 and significant apoptosis. These data suggest that phosphorylation of PDGF-R stimulates survival pathways in bone endothelial cells and that by selectively inhibiting PDGF-R signaling with STI571, the cells are rendered sensitive to Taxol treatment. The therapeutic combination of STI571 and Taxol may be a powerful tool for targeting tumor-associated endothelial cells in the skeletal compartment.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
64
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3727-30
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Activation of the platelet-derived growth factor-receptor enhances survival of murine bone endothelial cells.
pubmed:affiliation
Department of Cancer Biology, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.