摘要：

The epsin group of proteins, conserved from yeast, is expressed in two main forms in mammals: epsin 1 and epsin 2. These proteins play key roles in clathrin-mediated endocytosis and the activation of notch signaling. Specifically, the N-terminal of the protein containing ubiquitin interaction motifs (UIMs) allows epsin to regulate signal transmission of Vascular Endothelial Growth Factor (VEGF), a signal molecule that tumor cells use to stimulate angiogenesis. VEGFR-2 is the receptor protein for this signal molecule, and epsin is crucial in endocytosis that internalizes VEGFR-2, thus affecting the growth of tumors. Past breeding experiments have shown that mouse embryos with modi-fied genes which delete both forms of epsin are not viable past around E10, the early stages of organogenesis, due to disruption of notch signaling and vascular structure, but mice with only one of the two forms of epsin deleted experience no adverse phenotypic effects. Post-natal mice may be in-duced into "double knockouts" with drugs such as tamoxifen; this allows scientists to study the effects of a complete lack of epsin on the growth of various tumors. In this project we hypothesized that mice with a double knockout of epsin would experience inhibited melanoma and glioma tumor growth and angiogenesis, and we were particularly interested in the effects of an endothelial-cell-specific induc-ible knockout regulated by Vascular Endothelial Cadherin (VE-Cad). Both the VE-Cad knockout and the global tamoxifen knockout mice compared to wild type mice experienced inhibited tumor growth due to deregulated tumor angiogenesis, thus, leading to hypoxia of the tumor and apop-tosis of the tumor cells. These results reveal the role that epsin plays in the development and progression of tumors via controlling tumor angiogenesis.

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