The Role of BMI1 in CRPC
Technical Report,21 Sep 2015,20 Sep 2016
Methodist Hospital Research Institute Houston United States
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Our preliminary data strongly suggest that BMI1 is a master regulator of castration-resistant prostate cancer CRPC progression. Our objective is to determine how BMI interacts with epigenetic complexes and with AR to regulate tumor suppressor gene expression. We aim to identify novel binding partners and regulators of oncogene expression, which will lead to a better understanding of AR signaling and dysfunction. Specifically, we will identify how BMI1 and PRC1 proteins mediate their oncogenic functions by recruiting AR and distinct binding partners to promote castration-resistance of PCa. Furthermore, we will evaluate the therapeutic efficacy of targeting BMI1 and of combinational targeting of BMI1 and AR in castration-resistant prostate cancer. During the first year of this project, we discovered that BMI1 directly binds to Androgen Receptor and prevents it from MDM2-mediated protein degradation. We further demonstrated that inhibiting BMI1 decreased prostate cancer tumor growth in VCaP murine xenograft.