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An Antiangiogenic Network

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Science  26 Mar 2004:
Vol. 303, Issue 5666, pp. 1949
DOI: 10.1126/science.303.5666.1949c

Endostatin is an endogenous peptide that inhibits endothelial cell proliferation, migration, and tube formation. Abdollahi et al. performed DNA and antibody microarray analysis along with selected Western blotting and immunocytochemistry to show that endostatin regulates multiple pathways in human dermal microvascular endothelial cells. Endostatin displayed a broad effect on gene expression, with genes associated with the promotion of angiogenesis generally being down-regulated and genes associated with stress responses being up-regulated. The antibody arrays showed that for many of the pathways, the phosphorylation status of individual proteins was altered by endostatin treatment. Eight signaling cascades that were down-regulated by endostatin treatment were investigated in more detail: Id signaling and activator protein 1 (AP-1) signaling (cell proliferation), hypoxia-inducible factor 1α (HIF-1α) signaling (low oxygen and metabolic adaptation), ephrin and tumor necrosis factor-α (TNF-α) signaling (cell migration), nuclear factor κB (NF-κB) (proliferation and antiapoptosis), signal transducer and activator of transcription (STAT) signaling (regulator of proliferation and migration), Ets (migration and antiapoptosis), coagulation cascades, and adhesion molecule pathways. These results identify several new pathways regulated by endostatin and present a picture of a complex network of responses to a single ligand. — NG

Mol. Cell 13, 649 (2004).

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