The Ets family contains transcriptional activators and repressors involved in angiogenesis

Lelièvre, Etienne; Lionneton, Frédéric; Soncin, Fabrice; Vandenbunder, Bernard

doi:10.1016/s1357-2725(01)00025-5

Cited by 140 publications

(110 citation statements)

References 90 publications

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“…The early vascular expression of members of the ETS family of transcriptional regulators suggested they might be important for endothelial specification (Lelievre et al 2001). ETS factors can induce expression of endothelial specific genes such as flk1/vegfr2 and vascular endothelial cadherin (vecdn), and loss of function for these factors causes defects in endothelial cell behavior (Wakiya et al 1996;Chen et al 1997;Lelievre et al 2000;Nakano et al 2000).…”

Section: Origin and Specification Of Endothelial Precursorsmentioning

confidence: 99%

Vascular Development in the Zebrafish

Gore¹,

Monzo²,

Young³

et al. 2012

Cold Spring Harbor Perspectives in Medicine

238

166

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The zebrafish has emerged as an excellent vertebrate model system for studying blood and lymphatic vascular development. The small size, external and rapid development, and optical transparency of zebrafish embryos are some of the advantages the zebrafish model system offers. Multiple well-established techniques have been developed for imaging and functionally manipulating vascular tissues in zebrafish embryos, expanding on and amplifying these basic advantages and accelerating use of this model system for studying vascular development. In the past decade, studies performed using zebrafish as a model system have provided many novel insights into vascular development. In this article we discuss the amenability of this model system for studying blood vessel development and review contributions made by this system to our understanding of vascular development.

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Section: Origin and Specification Of Endothelial Precursorsmentioning

confidence: 99%

Vascular Development in the Zebrafish

Gore¹,

Monzo²,

Young³

et al. 2012

Cold Spring Harbor Perspectives in Medicine

238

166

View full text Add to dashboard Cite

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“…Ets-1 has been originally isolated as the cellular progenitor of v-ets, a viral oncogene found in the genome of the E26 acute leukaemia retrovirus, and later shown to be expressed in endothelial cells during development and during angiogenesis in the adult. Expression of Ets-1 is, however, not restricted to the endothelium as it is also expressed in the lymphoid organs of neonatal and adult mice, in somites and migrating neural crest cells in the embryo and in stromal fibroblasts of invasive tumors (for review see Lelie`vre et al, 2001). Therefore, though Ets-1 is not specific to the endothelium, it is prominently expressed in endothelial cells during angiogenesis.…”

Section: Hif-2a Specifically Activates the Ve-cadherin Gene A Le Brasmentioning

confidence: 99%

HIF-2α specifically activates the VE-cadherin promoter independently of hypoxia and in synergy with Ets-1 through two essential ETS-binding sites

et al. 2007

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The mechanisms that are responsible for the restricted pattern of expression of the VE-cadherin gene in endothelial cells are not clearly understood. Regulation of expression is under the control of an approximately 140 bp proximal promoter that provides basal, nonendothelial specific expression. A larger region contained within the 2.5 kb genomic DNA sequence located ahead of the transcription start is involved in the specific expression of the gene in endothelial cells. We show here that the VE-cadherin promoter contains several putative hypoxia response elements (HRE) which are able to bind endothelial nuclear factors under normoxia. The VE-cadherin gene is not responsive to hypoxia but hypoxia-inducible factor (HIF)-2a specifically activates the promoter while HIF-1a does not. The HRE, that are involved in this activity have been identified. Further, we show that HIF2a cooperates with the Ets-1 transcription factor for activation of the VE-cadherin promoter and that this synergy is dependent on the binding of Ets-1 to DNA. This cooperative action of HIF-2a with Ets-1 most probably participates to the transcriptional regulation of expression of the gene in endothelial cells. This mechanism may also be involved in the expression of the VE-cadherin gene by tumor cells in the process of vascular mimicry.

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“…Similar to the Ets family of transcription factors, the role of the AP-1 transcription factor is well established in vascular biology (Lelievre et al, 2001). The AP-1 factor is a heterodimeric complex consisting of members of either the Jun, Fos, ATF or Maf families of transcription factors (Eferl and Wagner, 2003).…”

Section: Introductionmentioning

confidence: 99%

CD13/APN transcription is regulated by the proto-oncogene c-Maf via an atypical response element

Mahoney

Petrović

Schacke

et al. 2007

Gene

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Angiogenic growth factors induce the transcription of the cell surface peptidase CD13/APN in activated endothelial cells of the tumor vasculature. Inhibition of CD13/APN abrogates endothelial invasion and morphogenesis in vitro and tumor growth in vivo suggesting a critical functional role for CD13 in angiogenesis. Experiments to identify the transcription factors responsible for this regulation demonstrated that exogenous expression of the proto-oncogene c-Maf, but not other bZip family members tested, potently activates transcription from a critical regulatory region of the CD13 proximal promoter between −115 and −70 bp which is highly conserved among mammalian species. Using promoter mutation, EMSA and ChIP analyses we established that both endogenous and recombinant c-Maf directly interact with an atypical Maf response element contained within this active promoter region via its basic DNA/leucine zipper domain. However full activity of c-Maf requires the amino-terminal transactivation domain, and site-directed mutation of putative phosphorylation sites within the transactivation domain (serines 15 and 70) shows that these sites behave in a dramatic cell type-specific manner. Therefore, this atypical response element predicts a broader range of c-Maf target genes than previously appreciated and thus impacts its regulation of multiple myeloma as well as endothelial cell function and angiogenesis.

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The Ets family contains transcriptional activators and repressors involved in angiogenesis

Cited by 140 publications

References 90 publications

Vascular Development in the Zebrafish

Vascular Development in the Zebrafish

HIF-2α specifically activates the VE-cadherin promoter independently of hypoxia and in synergy with Ets-1 through two essential ETS-binding sites

CD13/APN transcription is regulated by the proto-oncogene c-Maf via an atypical response element

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