Id1 Restrains p21 Expression to Control Endothelial Progenitor Cell Formation

Ciarrocchi, A., Jankovic, V., Shaked, Y., Nolan, D. J., Mittal, V., Kerbel, R. S., Nimer, S. D., Benezra, R. (2007) Id1 Restrains p21 Expression to Control Endothelial Progenitor Cell Formation. PLoS ONE, 2 (12). e1338. ISSN 1932-6203 (Electronic)

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URL: https://www.ncbi.nlm.nih.gov/pubmed/18092003
DOI: 10.1371/journal.pone.0001338

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.

Item Type: Paper
Additional Information:
Subjects: diseases & disorders > cancer
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > Id1
diseases & disorders > cancer > angiogenesis
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > p21
CSHL Authors:
Communities: CSHL labs > Mittal lab
Depositing User: CSHL Librarian
Date: 2007
Date Deposited: 30 Nov 2011 19:52
Last Modified: 22 Mar 2018 16:11
PMCID: PMC2129121
Related URLs:
URI: http://repository.cshl.edu/id/eprint/22989

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