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PMID: 9314544 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Induction of the angiogenic phenotype by Hox D3.

The Journal of cell biology ·Vol. 139 ·No. 1 ·1997-10-06 ·Pages 257-64

Boudreau N, Andrews C, Srebrow A, Ravanpay A, Cheresh DA

Abstract

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 alphavbeta3, and the urokinase plasminogen activator (uPA). Hox D3 antisense blocked the ability of bFGF to induce uPA and integrin alphavbeta3 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 alphavbeta3 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 regulates EC gene expression associated with the invasive stage of angiogenesis.

MeSH Terms
Animals Antigens, CD/biosynthesis,genetics Cell Division/genetics Cells, Cultured Chick Embryo Cyclin D1/biosynthesis DNA-Binding Proteins Endothelium, Vascular/cytology,pathology,physiology Fibroblast Growth Factor 2/physiology Gene Expression Regulation/physiology Genes, Homeobox Hemangioendothelioma/etiology,genetics Homeodomain Proteins/genetics,physiology Humans Integrin beta3 Integrins/biosynthesis,genetics Neovascularization, Pathologic/genetics Neovascularization, Physiologic/genetics Phenotype Platelet Membrane Glycoproteins/biosynthesis,genetics RNA, Messenger/biosynthesis Transcription Factors Urokinase-Type Plasminogen Activator/biosynthesis,genetics
Chemicals
Antigens, CD DNA-Binding Proteins Homeodomain Proteins Integrin beta3 Integrins Platelet Membrane Glycoproteins RNA, Messenger Transcription Factors Fibroblast Growth Factor 2 HOXA4 protein, human Cyclin D1 Urokinase-Type Plasminogen Activator
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Boudreau N
Department of Immunology and Vascular Biology, The Scripps Research Institute, La Jolla, California 92037, USA. [email protected]
Andrews C
Srebrow A
Ravanpay A
Cheresh D A
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.139.1.257
Email
[email protected]
Published
1997-10-06
Pages
257-64
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2139816
Subset
IM
Grants
NHLBI NIH HHS · HL54444 · United States
External Links
PubMed source DOI: 10.1083/jcb.139.1.257 PMC Full Text View journal details
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