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* Department of Immunology and Vascular Biology, The Scripps Research Institute, La Jolla, California 92037; and 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
Life Sciences Division, Ernest Orlando Lawrence Berkeley National Laboratory, Berkeley, California 94720
v
3, and the
urokinase plasminogen activator (uPA). Hox D3 antisense blocked the ability of bFGF to induce uPA and
integrin
v
3 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
v
3 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.
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