The Role of BMI1 in CRPC
Abstract
Cancer results from defects in many cellular functions and pathways, including the maintenance of genetic memory, which is important for cellular identity. The Polycomb Group (PcG) proteins play a major role in maintaining genetic memory and cellular identity. They are also known to be involved in cancer initiation and progression. We have discovered that BMI1, a member of the PcG family of proteins, is overexpressed in prostate cancer, particularly in aggressive and/or metastatic prostate cancers. Importantly, prostate cancer patients with high BMI1 levels have worse clinical outcomes compared with patients with low BMI1 expression. Furthermore, there is a significant body of evidence indicating that dysregulated BMI1 and other PcG proteins, along with the hormone-regulated androgen receptor (AR), contribute to prostate cancer development and progression. This proposal outlines our plan to explore the functional relationship between BMI1 (and other PcG proteins) and AR, which may cause prostate cancer. In this project, we will characterize the novel BMI1:AR complex, and dissect how BMI1 regulates oncoproteins via distinct co-factors in castration-resistant prostate cancer. Finally, we will test the newly developed BMI1 inhibitors and AR antagonists in PCa cells, and we will use animal models to determine whether inhibiting BMI1 (along with AR) kill PCa cells and inhibit tumor growth. Once this project is completed, we will have new insights into the cellular mechanisms of prostate cancer development, including disease initiation and progression. If our hypotheses are correct, we will have a strong rationale to develop therapies using BMI1 inhibitors for prostate cancer treatment.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Apr 04, 2016
- Source ID
- W81XWH1510639
Entities
People
- Qi Cao
Organizations
- Houston Methodist Research Institute
- United States Army