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ONCOGENES P3K AND AKT IN TUMORIGENESIS

$26,426F32FY2000CANIH

Scripps Research Institute, La Jolla CA

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Abstract

The objective of this research proposal is to characterize the oncogenes p3k and akt, and to provide a molecular explanation for the remarkable tissue specificity of tumor induced by P3k and Akt overexpression. This study will generate information on the mechanisms by which P3k and Akt induce cell transformation and tumors in chicken, and provide new insights into the mechanisms of angiogenesis during tumorigenesis. The specific aims of the proposal are: 1. Study the role of P3k and Akt in angiogenesis in vivo. The experiments will determine whether P3k and Akt induce angiogenesis, and study the mechanism of the angiogenesis induced by P3k and Akt. 2. Determine the transforming properties of P3k and Akt in specific cell types. The studies will determine whether P3k and Akt overexpression can affect specific cell types, and provide the explanation of the tumor specificity induced by P3k and Akt. 3. Test whether P3k and Akt mediate the expression of vascular endothelial growth factor (VEGF) and other angiogenic factors. The experiments will determine whether P3k and Akt can mediate VEGF expression, study whether the function of VEGF is required for P3k-and Akt-induced angiogenesis, test whether P3k and Akt affect the expression of other angiogenic factors, and study the signal transduction pathway of the P3k-and Akt- induced angiogenesis.

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