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. |