The Role of Polycomb Proteins in Prostate Cancer Progression
Authors:
Lizbeth Alvarez, Daniell Davis , Christine Doronio , Veronica MaganaMentor:
Luiza Nogaj , Dr. , Mount St. Mary's CollegeThe Polycomb proteins (PcG) function as transcriptional repressors and are thought to prevent the transcription of tumor suppressor genes such as p16. The p16 protein is known to prevent the proliferation of cell growth and directs the cell into apoptosis. However, the mechanism of Polycomb-mediated silencing of p16 and its connection to prostate cancer progression is still not well understood. Polycomb complexes are composed of many proteins, but we focus our attention on Bmi-1, Mel 18, Ring1A, and Rnf2. Previous work suggests that Ring1A and Rnf2 are ubiquitin ligases and their activity is regulated by Bmi1 and Mel18 (Elderkin et al., 2007, Wei et al., 2006).We study the role of the Polycomb complexes on the progression of prostate cancer. We are examining the levels of Bmi1, Mel18, Ring1A, Rnf2, and p16 in biopsy samples from different stages of prostate cancer. Our results show that the levels of Ring1A are increasing as the prostate cancer progresses. However, the levels of Rnf2 stay the same. We also observe an inverse relationship between Bmi-1 and Mel-18 levels. In malignant tumors, there is an over expression of Bmi-1 and an under expression of Mel-18 while the p16 protein cannot be detected. Based on these results, we hypothesize that Polycomb complexes change as the tumor progresses. The increasing amounts of Bmi1 and /or decreasing amounts of Mel18 in malignant tumors may increase the ubiquitin activity of Ring 1A and Rnf2. To test this hypothesis, we cloned, overexpressed, and purified Ring1A and Rnf2 as well as Bmi1 and Mel18. Our preliminary data suggest that the prsence of Bmi1 prevents polymerase from binding to the p16 promoter. The presence of Mel18 does not have the same effect. Further experiments are necessary to determine the effect of Bmi1 and Mel18 on the Ring1A and Rnf2 activities.