C-Myc expression in adult and embryonic endothelial cells
Auch gedruckt in der BibliothekZ: J-H 13.868; W: W-H 12.336
FakultätFakultät für Naturwissenschaften
Ressourcen- / MedientypDissertation, Text
Datum der Freischaltung2010-12-07
Previous work has shown that c-Myc is required for adequate vasculogenesis and angiogenesis. To further investigate the contribution of Myc to these processes, we conditionally expressed c-Myc in embryonic and adult endothelial cells using a tetracycline-regulated system. Vascular endothelial cell-specific overexpression of c-Myc in adult mice induced pathological malformations resulting in angiosarcomas and/or adenomas. Starting from week 22 adult double transgenic mice developed tumors and died in average with 36 weeks. Inactivation of the transgene system by doxycycline in vivo results in partial tumor regression. Endothelial Myc over-expression during embryonic development resulted in severe defects in the vascular system. Myc expressing embryos suffer from widespread edema formation and multiple hemorrhagic lesions. They die between embryonic day (E) E14.5 and E17.5. The changes in vascular permeability are not caused by deficiencies in vascular basement membrane composition or pericyte coverage. However, the overall turnover of endothelial cells is elevated as is revealed by increased levels of both proliferation and apoptosis. Whole mount immunohistochemical analysis revealed alterations in the architecture of capillary networks. The dermal vasculature of Myc expressing embryos is characterized by a reduction in vessel branching, which occurs despite up-regulation of the pro-angiogenic factors VEGF-A and angiopoietin-2 (Ang-2). Thus, the net outcome of an excess of VEGF-A and Ang-2 in the face of an elevated cellular turnover appears to be a defect in vascular integrity.
LizenzStandard (Fassung vom 01.10.2008)
Vascular endothelial growth factor A