Id1 regulates angiogenesis through transcriptional repression of thrombospondin-1

Olga V. Volpert, Roberto Pili, Hashmat A. Sikder, Thomas Nelius, Tetiana Zaichuk, Chad Morris, Clinton B. Shiflett, Meghann K. Devlin, Katherine Conant, Rhoda M. Alani

Research output: Contribution to journalArticlepeer-review

161 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)473-483
Number of pages11
JournalCancer Cell
Volume2
Issue number6
DOIs
StatePublished - Dec 2002

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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