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c-Myc is essential for vasculogenesis and angiogenesis during development and tumor progression

By Troy A. Baudino, Catriona McKay, Helene Pendeville-Samain, Jonas A. Nilsson, Kirsteen H. Maclean, Elsie L. White, Ann C. Davis, James N. Ihle and John L. Cleveland

Abstract

c-Myc promotes cell growth and transformation by ill-defined mechanisms. c-myc(−/−) mice die by embryonic day 10.5 (E10.5) with defects in growth and in cardiac and neural development. Here we report that the lethality of c-myc(−/−) embryos is also associated with profound defects in vasculogenesis and primitive erythropoiesis. Furthermore, c-myc(−/−) embryonic stem (ES) and yolk sac cells are compromised in their differentiative and growth potential. These defects are intrinsic to c-Myc, and are in part associated with a requirement for c-Myc for the expression of vascular endothelial growth factor (VEGF), as VEGF can partially rescue these defects. However, c-Myc is also required for the proper expression of other angiogenic factors in ES and yolk sac cells, including angiopoietin-2, and the angiogenic inhibitors thrombospondin-1 and angiopoietin-1. Finally, c-myc(−/−) ES cells are dramatically impaired in their ability to form tumors in immune-compromised mice, and the small tumors that sometimes develop are poorly vascularized. Therefore, c-Myc function is also necessary for the angiogenic switch that is indispensable for the progression and metastasis of tumors. These findings support the model wherein c-Myc promotes cell growth and transformation, as well as vascular and hematopoietic development, by functioning as a master regulator of angiogenic factors

Topics: Research Paper
Publisher: Cold Spring Harbor Laboratory Press
Year: 2002
DOI identifier: 10.1101/gad.1024602
OAI identifier: oai:pubmedcentral.nih.gov:187450
Provided by: PubMed Central
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