Induction of the Angiogenic Phenotype by Hox D3

Angiogenesis is characterized by distinct phenotypic changes in vascular endothelial cells (EC). Evidence is provided that the Hox D3 homeobox gene mediates conversion of endothelium from the resting to the angiogenic/invasive state. Stimulation of EC with basic fibroblast growth factor (bFGF) resul...

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Bibliographic Details
Published in:The Journal of cell biology 1997-10, Vol.139 (1), p.257-264
Main Authors: Boudreau, Nancy, Andrews, Catherine, Srebrow, Anabella, Ravanpay, Ali, Cheresh, David A.
Format: Article
Language:English
Subjects:
Angiogenesis
Animals
Antigens, CD - biosynthesis
Antigens, CD - genetics
BASIC BIOLOGICAL SCIENCES
BLOOD VESSELS
Cell Division - genetics
Cell lines
Cells
Cells, Cultured
Cellular biology
Chick Embryo
Cyclin D1 - biosynthesis
DNA
DNA-Binding Proteins
Endothelial cells
Endothelium, Vascular - cytology
Endothelium, Vascular - pathology
Endothelium, Vascular - physiology
Fibroblast Growth Factor 2 - physiology
Gene Expression Regulation - physiology
Genes
Genes, Homeobox
Hemangioendothelioma - etiology
Hemangioendothelioma - genetics
Homeodomain Proteins - genetics
Homeodomain Proteins - physiology
Human umbilical vein endothelial cells
Humans
INDUCTION
Integrin beta3
Integrins
Integrins - biosynthesis
Integrins - genetics
Messenger RNA
Neovascularization, Pathologic - genetics
Neovascularization, Physiologic - genetics
PHENOTYPE
Platelet Membrane Glycoproteins - biosynthesis
Platelet Membrane Glycoproteins - genetics
RNA
RNA, Messenger - biosynthesis
Urokinase-Type Plasminogen Activator - biosynthesis
Urokinase-Type Plasminogen Activator - genetics
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Summary:Angiogenesis is characterized by distinct phenotypic changes in vascular endothelial cells (EC). Evidence is provided that the Hox D3 homeobox gene mediates conversion of endothelium from the resting to the angiogenic/invasive state. Stimulation of EC with basic fibroblast growth factor (bFGF) resulted in increased expression of Hox D3, integrin αvβ3, and the urokinase plasminogen activator (uPA). Hox D3 antisense blocked the ability of bFGF to induce uPA and integrin αvβ3 expression, yet had no effect on EC cell proliferation or bFGF-mediated cyclin D1 expression. Expression of Hox D3, in the absence of bFGF, resulted in enhanced expression of integrin αvβ3 and uPA. In fact, sustained expression of Hox D3 in vivo on the chick chorioallantoic membrane retained EC in this invasive state and prevented vessel maturation leading to vascular malformations and endotheliomas. Therefore, Hox D3 regulated EC gene expression associated with the invasive stage of angiogenesis.
ISSN:0021-9525
1540-8140
DOI:10.1083/jcb.139.1.257