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Publication : Id1 restrains p21 expression to control endothelial progenitor cell formation.

First Author  Ciarrocchi A Year  2007
Journal  PLoS One Volume  2
Issue  12 Pages  e1338
PubMed ID  18092003 Mgi Jnum  J:129227
Mgi Id  MGI:3768899 Doi  10.1371/journal.pone.0001338
Citation  Ciarrocchi A, et al. (2007) Id1 Restrains p21 Expression to Control Endothelial Progenitor Cell Formation. PLoS One 2(12):e1338
abstractText  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.
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