J. Cell Biol.
© The Rockefeller University Press
0021-9525/97/10/257/08 $2.00
Volume 139, Number 1, October 6, 1997 257-264

Induction of the Angiogenic Phenotype by Hox D3

Nancy Boudreau,^* Catherine Andrews,^* Anabella Srebrow, Ali Ravanpay, and David A. Cheresh^*

^*  Department of Immunology and Vascular Biology, The Scripps Research Institute, La Jolla, California 92037; and   Life Sciences Division, Ernest Orlando Lawrence Berkeley National Laboratory, Berkeley, California 94720

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 v3, and the urokinase plasminogen activator (uPA). Hox D3 antisense blocked the ability of bFGF to induce uPA and integrin v3 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 v3 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.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Beauvais, D. M., Ell, B. J., McWhorter, A. R., Rapraeger, A. C. (2009). Syndecan-1 regulates {alpha}v{beta}3 and {alpha}v{beta}5 integrin activation during angiogenesis and is blocked by synstatin, a novel peptide inhibitor. JEM 206: 691-705 [Abstract] [Full Text]  
• Chen, Y., Gorski, D. H. (2008). Regulation of angiogenesis through a microRNA (miR-130a) that down-regulates antiangiogenic homeobox genes GAX and HOXA5. Blood 111: 1217-1226 [Abstract] [Full Text]  
• Pascual-Castroviejo, I., Pascual-Pascual, S.-I., Lopez-Gutierrez, J.-C., Velazquez-Fragua, R., Viano, J. (2007). Facial Hemangioma and Hemispheric Migration Disorder: Presentation of 5 Patients. Am. J. Neuroradiol. 28: 1609-1612 [Abstract] [Full Text]  
• Bandyopadhyay, S., Ashraf, M. Z., Daher, P., Howe, P. H., DiCorleto, P. E. (2007). HOXA9 Participates in the Transcriptional Activation of E-Selectin in Endothelial Cells. Mol. Cell. Biol. 27: 4207-4216 [Abstract] [Full Text]  
• Diehl, F., Rossig, L., Zeiher, A. M., Dimmeler, S., Urbich, C. (2007). The histone methyltransferase MLL is an upstream regulator of endothelial-cell sprout formation. Blood 109: 1472-1478 [Abstract] [Full Text]  
• Chen, Y., Leal, A. D., Patel, S., Gorski, D. H. (2007). The Homeobox Gene GAX Activates p21WAF1/CIP1 Expression in Vascular Endothelial Cells through Direct Interaction with Upstream AT-rich Sequences. J. Biol. Chem. 282: 507-517 [Abstract] [Full Text]  
• Hamik, A., Wang, B., Jain, M. K. (2006). Transcriptional Regulators of Angiogenesis. Arterioscler. Thromb. Vasc. Bio. 26: 1936-1947 [Abstract] [Full Text]  
• Zhang, G., Fahmy, R. G., diGirolamo, N., Khachigian, L. M. (2006). JUN siRNA regulates matrix metalloproteinase-2 expression, microvascular endothelial growth and retinal neovascularisation. J. Cell Sci. 119: 3219-3226 [Abstract] [Full Text]  
• Lei, H., Juan, A. H., Kim, M.-S., Ruddle, F. H. (2006). Identification of a Hoxc8-regulated transcriptional network in mouse embryo fibroblast cells. Proc. Natl. Acad. Sci. USA 103: 10305-10309 [Abstract] [Full Text]  
• van Nes, J., de Graaff, W., Lebrin, F., Gerhard, M., Beck, F., Deschamps, J. (2006). The Cdx4 mutation affects axial development and reveals an essential role of Cdx genes in the ontogenesis of the placental labyrinth in mice. Development 133: 419-428 [Abstract] [Full Text]  
• Carrio, M., Arderiu, G., Myers, C., Boudreau, N. J. (2005). Homeobox D10 Induces Phenotypic Reversion of Breast Tumor Cells in a Three-Dimensional Culture Model. Cancer Res. 65: 7177-7185 [Abstract] [Full Text]  
• Mace, K. A., Hansen, S. L., Myers, C., Young, D. M., Boudreau, N. (2005). HOXA3 induces cell migration in endothelial and epithelial cells promoting angiogenesis and wound repair. J. Cell Sci. 118: 2567-2577 [Abstract] [Full Text]  
• Ihida-Stansbury, K., McKean, D. M., Gebb, S. A., Martin, J. F., Stevens, T., Nemenoff, R., Akeson, A., Vaughn, J., Jones, P. L. (2004). Paired-Related Homeobox Gene Prx1 Is Required for Pulmonary Vascular Development. Circ. Res. 94: 1507-1514 [Abstract] [Full Text]  
• Bruhl, T., Urbich, C., Aicher, D., Acker-Palmer, A., Zeiher, A. M., Dimmeler, S. (2004). Homeobox A9 Transcriptionally Regulates the EphB4 Receptor to Modulate Endothelial Cell Migration and Tube Formation. Circ. Res. 94: 743-751 [Abstract] [Full Text]  
• Leroy, P., Berto, F., Bourget, I., Rossi, B. (2004). Down-regulation of Hox A7 is required for cell adhesion and migration on fibronectin during early HL-60 monocytic differentiation. J. Leukoc. Biol. 75: 680-688 [Abstract] [Full Text]  
• Boudreau, N. J., Varner, J. A. (2004). The Homeobox Transcription Factor Hox D3 Promotes Integrin {alpha}5{beta}1 Expression and Function during Angiogenesis. J. Biol. Chem. 279: 4862-4868 [Abstract] [Full Text]  
• Hansen, S. L., Myers, C. A., Charboneau, A., Young, D. M., Boudreau, N. (2003). HoxD3 Accelerates Wound Healing in Diabetic Mice. Am. J. Pathol. 163: 2421-2431 [Abstract] [Full Text]  
• Pollet, I., Opina, C. J., Zimmerman, C., Leong, K. G., Wong, F., Karsan, A. (2003). Bacterial lipopolysaccharide directly induces angiogenesis through TRAF6-mediated activation of NF-{kappa}B and c-Jun N-terminal kinase. Blood 102: 1740-1742 [Abstract] [Full Text]  
• Wu, Y., Moser, M., Bautch, V. L., Patterson, C. (2003). HoxB5 Is an Upstream Transcriptional Switch for Differentiation of the Vascular Endothelium from Precursor Cells. Mol. Cell. Biol. 23: 5680-5691 [Abstract] [Full Text]  
• McKean, D. M., Sisbarro, L., Ilic, D., Kaplan-Alburquerque, N., Nemenoff, R., Weiser-Evans, M., Kern, M. J., Jones, P. L. (2003). FAK induces expression of Prx1 to promote tenascin-C-dependent fibroblast migration. JCB 161: 393-402 [Abstract] [Full Text]  
• Nakagawa, T., Abe, M., Yamazaki, T., Miyashita, H., Niwa, H., Kokubun, S., Sato, Y. (2003). HEX Acts as a Negative Regulator of Angiogenesis by Modulating the Expression of Angiogenesis-Related Gene in Endothelial Cells In Vitro. Arterioscler. Thromb. Vasc. Bio. 23: 231-237 [Abstract] [Full Text]  
• Schmidt, E. V. (2002). Genes Involved in Breast Cancer Progression: Analysis of Global Changes in Gene Expression or Retroviral Tagging?. Am. J. Pathol. 161: 1973-1977 [Full Text]  
• Myers, C., Charboneau, A., Cheung, I., Hanks, D., Boudreau, N. (2002). Sustained Expression of Homeobox D10 Inhibits Angiogenesis. Am. J. Pathol. 161: 2099-2109 [Abstract] [Full Text]  
• Alliegro, M. C., Alliegro, M. A. (2002). Nuclear Injection of Anti-pigpen Antibodies Inhibits Endothelial Cell Division. J. Biol. Chem. 277: 19037-19041 [Abstract] [Full Text]  
• Leong, K. G., Hu, X., Li, L., Noseda, M., Larrivee, B., Hull, C., Hood, L., Wong, F., Karsan, A. (2002). Activated Notch4 Inhibits Angiogenesis: Role of {beta}1-Integrin Activation. Mol. Cell. Biol. 22: 2830-2841 [Abstract] [Full Text]  
• Stupack, D. G., Cheresh, D. A. (2002). ECM Remodeling Regulates Angiogenesis: Endothelial Integrins Look for New Ligands. Sci Signal 2002: pe7-pe7 [Abstract] [Full Text]  
• Urbich, C., Dernbach, E., Reissner, A., Vasa, M., Zeiher, A. M., Dimmeler, S. (2002). Shear Stress-Induced Endothelial Cell Migration Involves Integrin Signaling Via the Fibronectin Receptor Subunits {alpha}5 and {beta}1. Arterioscler. Thromb. Vasc. Bio. 22: 69-75 [Abstract] [Full Text]  
• Gadd, M., Pisc, C., Branda, J., Ionescu-Tiba, V., Nikolic, Z., Yang, C., Wang, T., Shackleford, G. M., Cardiff, R. D., Schmidt, E. V. (2001). Regulation of Cyclin D1 and p16INK4A Is Critical for Growth Arrest during Mammary Involution. Cancer Res. 61: 8811-8819 [Abstract] [Full Text]  
• Care, A., Felicetti, F., Meccia, E., Bottero, L., Parenza, M., Stoppacciaro, A., Peschle, C., Colombo, M. P. (2001). HOXB7: A Key Factor for Tumor-associated Angiogenic Switch. Cancer Res. 61: 6532-6539 [Abstract] [Full Text]  
• Oettgen, P. (2001). Transcriptional Regulation of Vascular Development. Circ. Res. 89: 380-388 [Abstract] [Full Text]  
• Woods, D., Cherwinski, H., Venetsanakos, E., Bhat, A., Gysin, S., Humbert, M., Bray, P. F., Saylor, V. L., McMahon, M. (2001). Induction of {beta}3-Integrin Gene Expression by Sustained Activation of the Ras-Regulated Raf-MEK-Extracellular Signal-Regulated Kinase Signaling Pathway. Mol. Cell. Biol. 21: 3192-3205 [Abstract] [Full Text]  
• Conway, E. M., Collen, D., Carmeliet, P. (2001). Molecular mechanisms of blood vessel growth. Cardiovasc Res 49: 507-521 [Full Text]  
• Gorski, D. H., Walsh, K. (2000). The Role of Homeobox Genes in Vascular Remodeling and Angiogenesis. Circ. Res. 87: 865-872 [Abstract] [Full Text]  
• Myers, C., Charboneau, A., Boudreau, N. (2000). Homeobox B3 Promotes Capillary Morphogenesis and Angiogenesis. JCB 148: 343-352 [Abstract] [Full Text]  
• Patel, C. V., Sharangpani, R., Bandyopadhyay, S., DiCorleto, P. E. (1999). Endothelial Cells Express a Novel, Tumor Necrosis Factor-alpha -regulated Variant of HOXA9. J. Biol. Chem. 274: 1415-1422 [Abstract] [Full Text]  
• Eliceiri, B. P., Klemke, R., Stromblad, S., Cheresh, D. A. (1998). Integrin alpha vbeta 3 Requirement for Sustained Mitogen-activated Protein Kinase Activity during Angiogenesis. JCB 140: 1255-1263 [Abstract] [Full Text]  
• Hashimoto, T., Lam, T., Boudreau, N. J., Bollen, A. W., Lawton, M. T., Young, W. L. (2001). Abnormal Balance in the Angiopoietin-Tie2 System in Human Brain Arteriovenous Malformations. Circ. Res. 89: 111-113 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents