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) 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.
Boudreau
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N
Department of Immunology and Vascular Biology, The Scripps Research Institute, La Jolla, California 92037, USA. nboudrea@nsc.vcu.edu
Andrews
C
C
Srebrow
A
A
Ravanpay
A
A
Cheresh
D A
DA
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D002478:Cells, Cultured; D002642:Chick Embryo; D019938:Cyclin D1 / Q000096:biosynthesis; D004268:DNA-Binding Proteins; D004730:Endothelium, Vascular / Q000166:cytology / Q000473:pathology / Q000502:physiology; D016222:Fibroblast Growth Factor 2 / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology; D005801:Genes, Homeobox; D006390:Hemangioendothelioma / Q000209:etiology / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D006801:Humans; D039661:Integrin beta3; D016023:Integrins / Q000096:biosynthesis / Q000235:genetics; D009389:Neovascularization, Pathologic / Q000235:genetics; D018919:Neovascularization, Physiologic / Q000235:genetics*; D010641:Phenotype; D010980:Platelet Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D014157:Transcription Factors; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis / Q000235:genetics
D015703:Antigens, CD; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D039661:Integrin beta3; D016023:Integrins; D010980:Platelet Membrane Glycoproteins; D012333:RNA, Messenger; D014157:Transcription Factors; D016222:Fibroblast Growth Factor 2; C073547:HOXA4 protein, human; D019938:Cyclin D1; D014568:Urokinase-Type Plasminogen Activator