Induction of vascular endothelial growth factor expression in endothelial cells by platelet-derived growth factor through the activation of phosphatidylinositol 3-kinase

Increased numbers of platelet-derived growth factor beta receptors betaPPDGFRs) on neovascular endothelial cells is a common occurrence in several pathological conditions including wound healing, inflammation, and glioma tumorigenesis. Here we sought to test the biological significance of this by de...

Full description

Saved in:
Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1999-04, Vol.59 (7), p.1464-1472
Main Authors: DEGUI WANG, HUANG, H.-J. S, KAZLAUSKAS, A, CAVENEE, W. K
Format: Article
Language:English
Subjects:
Biological and medical sciences
Cell physiology
Dose-Response Relationship, Drug
Endothelial Growth Factors - biosynthesis
Endothelial Growth Factors - genetics
Endothelium, Vascular - metabolism
Enzyme Activation
Fundamental and applied biological sciences. Psychology
Humans
Lymphokines - biosynthesis
Lymphokines - genetics
Molecular and cellular biology
Phosphatidylinositol 3-Kinases - physiology
Platelet-Derived Growth Factor - pharmacology
Responses to growth factors, tumor promotors, other factors
RNA, Messenger - analysis
Transcription, Genetic - drug effects
Up-Regulation
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factors
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Increased numbers of platelet-derived growth factor beta receptors betaPPDGFRs) on neovascular endothelial cells is a common occurrence in several pathological conditions including wound healing, inflammation, and glioma tumorigenesis. Here we sought to test the biological significance of this by determining whether expression of wild-type betaPDGFR by normal aortic endothelial cells affected the expression of the vascular endothelial growth factor (VEGF), a critical angiogenesis regulator and mitogen for such cells. The results showed that PDGF could increase transcription and secretion of VEGF by betaPDGFR-expressing endothelial cells. Moreover, we further demonstrated a requirement for the activation of phosphatidylinositol 3-kinase (PI3K) in this response by using chemical inhibitors of PI3K, mutant PDGFR, and dominant-negative PI3K. These studies suggest a novel mechanism by which PDGF induces VEGF expression in endothelial cells, define VEGF as a downstream target for PI3K, and invoke a role for PI3K in angiogenesis.
ISSN:0008-5472
1538-7445