Apoptosis-Dependent and Apoptosis-Independent Functions of Bim in Prostate Cancer Cells
Annual summary, 1 Mar 2003-28 Feb 2005
MD ANDERSON CANCER CENTER SMITHVILLE TX SCIENCE PARK RESEARCH DIV
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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 postdoctoral 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, proliferationdivision, etc.. Our hypothesis is that, under normal, unstimulated conditions, with its apoptotic function blocked, the upregulated Bim in PCa cells plays an apoptosis-independent functions. 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. The PI of the grant, Dr. Junwei Liu, had to leave the lab Oct. of 2004. Before he left, he had completed all experiments in Specific Aim 2 with one manuscript published Append. I. After he left, with the small amounts of funds left over from the Fellowship, we have just accomplished all of the experiments proposed in Specific Aim 1 and are in the process of preparing a manuscript, which will be supplied to DOD when it is ready.
- Medicine and Medical Research