Identification and Characterization of Distinct Apoptotic Pathways in Cancer Cells Activated in Response to Treatment with Different Anti-Cancer Agents

摘要

Apoptosis is a programmed form of cell death that plays an important role in malignancy by shifting the balance from tumor proliferation to its regression. Anticancer drugs act by activating apoptosis in tumor cells. Mutations in apoptotic pathways can lead to anticancer drug resistance and therefore can promote tumor progression. Anticancer agents ultimately induce apoptosis by activating caspases, a family of cystein proteases that are essential components of the cell death machinery. Caspases are expressed as latent pro-enzymes and processed to active enzymes during apoptotic cell death. These enzymes may play an important role in drug sensitivity and specific tumor suppression. The goal of my thesis project is to identify caspases that are involved in programmed cell death in primary MEFs, to identify caspases activated during distinct apoptotic programs, to determine the effect of oncogene (El A) expression on caspases in the cells and finally to establish the role of one particular caspase in distinct forms of apoptosis in oncogenically- transformed MEFs.