Author/Authors :
Volpert، نويسنده , , Olga V and Pili، نويسنده , , Roberto and Sikder، نويسنده , , Hashmat A and Nelius، نويسنده , , Thomas and Zaichuk، نويسنده , , Tetiana and Morris، نويسنده , , Chad and Shiflett، نويسنده , , Clinton B and Devlin، نويسنده , , Meghann K and Conant، نويسنده , , Katherine and Alani، نويسنده , , Rhoda M، نويسنده ,
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.
