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Publication : Id1 regulates angiogenesis through transcriptional repression of thrombospondin-1.

First Author  Volpert OV Year  2002
Journal  Cancer Cell Volume  2
Issue  6 Pages  473-83
PubMed ID  12498716 Mgi Jnum  J:81587
Mgi Id  MGI:2449676 Doi  10.1016/s1535-6108(02)00209-x
Citation  Volpert OV, et al. (2002) Id1 regulates angiogenesis through transcriptional repression of thrombospondin-1. Cancer Cell 2(6):473-83
abstractText  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.
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