Apoptosis-Dependent and Apoptosis-Independent Functions Bim in Prostate Cancer Cells

摘要

Attenuated apoptotic response and extended cell survival have been implicated in prostate cancer (PCa) development and progression. We recently found that Bim, a BH3-only pro- apoptotic protein, is upregulated in PCa cells in vitro and in vivo. The main objective of this post-doctoral fellowship is to elucidate why PCa cells upregulate Bim and what is the role of the upregulated Bim proteins in modulating PCa cell behavior (death, survival, proliferation/division, etc). Our hypothesis is that, under normal, unstimulated conditions, with its apoptotic function blocked, the upregulated Bim in PCa cells play an apoptosis-independent function(s). Under apoptosis- stimulated conditions, however, Bim can still participate in triggering a robust apoptotic response, thus guaranteeing that 'weaker' or 'more susceptible' PCa cells be eliminated from the population. Two Specific Aims were proposed to determine: (1) apoptosis-independent functions of the upregulated Bim in PCa cells under unstimulated conditions, and (2) apoptosis- dependent functions of the upregulated Bim in PCa cells under stimulated conditions. By now, we have completed all experiments in Specific Aim 2 with one manuscript published. Most of the experiments in Specific Aim I were accomplished when the PI, Dr. Junwei Liu, left the lab Oct of 2005. With the small amounts of funds left over from the Fellowship, we are now in the process of finishing up the rest of Specific Aim 1.