The long-term goal of this project is to determine the mechanism(s) by which autophagy contributes to tumor development, maintenance, and treatment. We will assess the role of autophagy in Myc-induced lymphoma development and maintenance. Beclin, a gene required for autophagy, is monoallelically deleted in approximately 70% of breast cancers and heterozygous deletion of Beclin leads to tumor development. Beclin heterozygosity can also co-operate with c-Myc over expression to increase the rate of tumor development (see preliminary data). This grant focuses on the role of autophagy in Myc-induced B-cell lymphoma. Specific aim 1 will further characterize the role of autophagy as a checkpoint in cancer development and determine its role in the cell cycle and apoptotic functions attributed to Myc overexpression. Specific aim 2 will address whether or not a minimal level of autophagy is required for tumor maintenance. It is suggested that a complete ablation of autophagy may be theraputic, and we will test this hypothesis genetically.