Bcl-2 Conformational Change as an Indicator of Chemotherapy Response

摘要

Most anticancer agents ultimately kill cancer cells primarily by inducing apoptosis a programmed cell death. We propose that Bcl-2 undergoes a conformational change in response to chemotherapeutic agents in breast cancer cells in vitro and in vivo and that a Bcl-2-conformation-sensitive antibody can be used to better predict and evaluate the responses of breast cancer cells to therapies. We have characterized an epitope-specific anti-Bcl-2 antibody that specific recognizes pro-apoptotic Bcl-2 conformation. By using this antibody, we show that a number of chemotherapeutic agents, including paclitaxel, retinoid-related molecules, and nonsteroidal anti-inflammatory drugs, induce breast cancer cell apoptosis by modulating Bcl-2 conformation. Induction of Bcl- 2 conformational change involves Bcl-2 phosphorylation. Moreover, apoptosis induction of breast tumor grown in animal by a Nur77-derived peptide correlates with Bcl-2 conformational change. Together, we have developed a novel epitope- specific anti-Bcl-2 antibody that can be used to predict and evaluate the response of breast cancer cells to certain chemotherapeutic agents in vitro and in animal.