Id1 restrains p21 expression to control endothelial progenitor cell formation Journal Article


Authors: Ciarrocchi, Alessia; Jankovic, Vladimir; Shaked, Yuval; Nolan, Daniel J.; Mittal, Vivek; Kerbel, Robert S.; Nimer, Stephen D; Benezra, Robert
Article Title: Id1 restrains p21 expression to control endothelial progenitor cell formation
Abstract: Loss of Id1 in the bone marrow (BM) severely impairs tumor angiogenesis resulting in significant inhibition of tumor growth. This phenotype has been associated with the absence of circulating endothelial progenitor cells (EPCs) in the peripheral blood of Id1 mutant mice. However, the manner in which Id1 loss in the BM controls EPC generation or mobilization is largely unknown. Using genetically modified mouse models we demonstrate here that the generation of EPCs in the BM depends on the ability of Id1 to restrain the expression of its target gene p21. Through a series of cellular and functional studies we show that the increased myeloid commitment of BM stem cells and the absence of EPCs in Id1 knockout mice are associated with elevated p21 expression. Genetic ablation of p21 rescues the EPC population in the Id1 null animals, re-establishing functional BM-derived angiogenesis and restoring normal tumor growth. These results demonstrate that the restraint of p21 expression by Id1 is one key element of its activity in facilitating the generation of EPCs in the BM and highlight the critical role these cells play in tumor angiogenesis.
Keywords: angiogenesis; cell formation
Journal Title: PLoS ONE
Volume: 2
Issue: 12
ISSN: 1932-6203
Publisher: Public Library of Science  
Date Published: 2007-12-19
Start Page: e1338
Language: English
ACCESSION: BIOSIS:PREV201000107782
DOI: 10.1371/journal.pone.0001338
PROVIDER: biosis
PMCID: PMC2129121
PUBMED: 18092003
DOI/URL:
Notes: --- - Article - "Source: Biosis"
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  1. Stephen D Nimer
    347 Nimer
  2. Robert Benezra
    146 Benezra