WEST VIRGINIA UNIVERSITY RESEARCH CORPORATION
The long-term objectives of this proposal is to understand the molecular mechanisms of prostate tumorigenesis due to deregulation of the P13K and PTEN pathway, and to elucidate the connection of P13K and PTEN downstream signaling components to tumor formation and growth. We hypothesize that P13K regulates prostate tumorigenesis by activating its downstream targets and mediator for inducing prostate tumorigenesis. Aim 1 is designed to identify the mechanisms and functions of P13K and PTEN that regulate prostate tumor growth using our established tumor. The title of RO1 project: P13K Pathway in ProstateTumorigenesis and Angiogenesis models. This aim will study the effects of P13K and PTEN in prostate tumor growth, test the role of P13K activation in inducing tumor growth, and search for function of P13K effector VEGF involved in prostate tumor formation and growth. Aim 2 is designed to characterize P13K downstream signaling molecules to transmit P13K signals for inducing prostate tumor growth. We will determine whether AKT transmits the oncogenic signals from the deregulation of P13K and PTEN signaling, and whether AKT in turn activates p70S6K1 and MDM2 in inducing prostate tumor growth. This work will identify new functions of P13K and P13K effectors in prostate tumor growth, reveal mechanisms of P13K signaling in regulating prostate tumor growth, and help to establish rational therapeutic strategies for human prostate cancer by targeting specific signaling molecules in the future.