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Blood, 1 April 2006, Vol. 107, No. 7, pp. 2705-2712. Prepublished online as a Blood First Edition Paper on November 22, 2005; DOI 10.1182/blood-2005-09-3541. This Article Full Text (PDF) All Versions of this Article: 2005-09-3541v1 107/7/2705    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Calvani, M. Articles by Melillo, G. Search for Related Content PubMed PubMed Citation Articles by Calvani, M. Articles by Melillo, G. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted September 1, 2005 Accepted November 10, 2005 Hypoxic induction of a HIF-1- dependent bFGF autocrine loop drives angiogenesis in human endothelial cells Maura Calvani, Annamaria Rapisarda, Badarch Uranchimeg, Robert H Shoemaker, and Giovanni Melillo* Developmental Therapeutics Program, National Cancer Institute at Frederick, Frederick, MD, USA Science Applications International Corporation, National Cancer Institute at Frederick, Frederick, MD, USA * Corresponding author; email: melillog{at}ncifcrf.gov. Hypoxia is a major pathophysiological condition for the induction of angiogenesis, which is a crucial aspect of growth in solid tumors. In mammalian cells the transcriptional response to oxygen deprivation is largely mediated by hypoxia inducible factor 1 (HIF-1), a heterodimer composed of HIF-1 and HIF- subunits. However, the response of endothelial cells to hypoxia and the specific involvement of HIF- subunits in this process are still poorly understood. We show that HUVECs cultured in the absence of growth factors survive and form tube-like structures only when cultured under hypoxic but not normoxic conditions. HUVECs expressed both HIF-1 and HIF-2 when cultured under hypoxic conditions. Transfection of HIF-1, but not HIF-2, siRNA to HUVECs completely abrogated hypoxic induction of cords. Neutralizing antibodies to bFGF, but not IGF-1, VEGF or PDGF-BB, blocked survival and sprouting of HUVECs under hypoxic conditions, suggesting the existence of an autocrine loop induced by low oxygen levels. Notably, bFGF-dependent induction of cord formation under normoxic conditions required HIF-1 activity, which was also essential for hypoxic induction of bFGF mRNA and protein expression. These results uncover the existence of a HIF-1-bFGF amplification pathway that mediates survival and sprouting of endothelial cells under hypoxic conditions. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. Martorell, M. Gentile, J. Rius, C. Rodriguez, J. Crespo, L. Badimon, and J. Martinez-Gonzalez The Hypoxia-Inducible Factor 1/NOR-1 Axis Regulates the Survival Response of Endothelial Cells to Hypoxia Mol. Cell. Biol., November 1, 2009; 29(21): 5828 - 5842. [Abstract] [Full Text] [PDF] C. K. Lau, Z. F. Yang, D. W. Ho, M. N. Ng, G. C.T. Yeoh, R. T.P. Poon, and S. T. Fan An Akt/Hypoxia-Inducible Factor-1{alpha}/Platelet-Derived Growth Factor-BB Autocrine Loop Mediates Hypoxia-Induced Chemoresistance in Liver Cancer Cells and Tumorigenic Hepatic Progenitor Cells Clin. Cancer Res., May 15, 2009; 15(10): 3462 - 3471. [Abstract] [Full Text] [PDF] T. Zhao, D. Wang, S. Y. Cheranov, M. Karpurapu, K. R. 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