PMID:12498716

Citation	Volpert, OV, Pili, R, Sikder, HA, Nelius, T, Zaichuk, T, Morris, C, Shiflett, CB, Devlin, MK, Conant, K and Alani, RM (2002) Id1 regulates angiogenesis through transcriptional repression of thrombospondin-1. Cancer Cell 2:473-83
Abstract	Id proteins are helix-loop-helix transcription factors that regulate tumor angiogenesis. In order to identify downstream effectors of Id1 involved in the regulation of angiogenesis, we performed PCR-select subtractive hybridization on wild-type and Id1 knockout mouse embryo fibroblasts (MEFs). Here we demonstrate that thrombospondin-1 (TSP-1), a potent inhibitor of angiogenesis, is a target of transcriptional repression by Id1. We also show that Id1-null MEFs secrete an inhibitor of endothelial cell migration, which is completely inactivated by depletion of TSP-1. Furthermore, in vivo studies revealed decreased neovascularization in matrigel assays in Id1-null mice compared to their wild-type littermates. This decrease was completely reversed by a TSP-1 neutralizing antibody. We conclude that TSP-1 is a major target for Id1 effects on angiogenesis.
Links	PubMed
Keywords	Animals; Cattle; Cell Movement/drug effects; Cells, Cultured; E-Box Elements; Embryo, Mammalian; Endothelium, Vascular/drug effects; Endothelium, Vascular/metabolism; Fibroblasts/physiology; Gene Expression Regulation; Humans; Immunohistochemistry; Inhibitor of Differentiation Protein 1; Mice; Mice, Knockout; Neovascularization, Pathologic/genetics; Polymerase Chain Reaction; Promoter Regions, Genetic; Repressor Proteins; Thrombospondin 1/antagonists & inhibitors; Thrombospondin 1/biosynthesis; Thrombospondin 1/genetics; Thrombospondin 1/pharmacology; Transcription Factors/deficiency; Transcription Factors/physiology; Transcription, Genetic; Up-Regulation
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