Defining the Role of Absent in Melanoma 1 (AIM1) in Aggressive Prostate Cancer
Abstract
Previously published data from our lab suggested that alterations in the novel actin binding protein AIM1 could be associated with prostate cancer progression and more aggressive biological behavior. In this reporting period, we have established numerous cell lines in which we have robustly depleted AIM1 by shRNAs and we have generated domain and mutation specific AIM1 expression vectors, which will allow us to study structure function relationships. Furthermore, we have investigated the frequency of germline genomic alterations in 4 large prostate cancer cohorts and observed an enrichment in deleterious germline mutations in men who developed metastatic disease. This observation provides first evidence that germline changes in genes involved in cytoskeletal organization can be associated with aggressive variants of prostate cancer. To corroborate this finding, we developed a novel genetically modified mouse model by crossing hi-MYC mice to Aim1(exp +/-) mice. These crosses yielded viable offspring and preliminary analyses suggest that constitutive Aim1 loss in this model results in accelerated tumor progression. We are currently expanding these cohorts to determine the impact of Aim1 loss at different timepoints. Collectively, these studies will provide important insights in the role of AIM1 and the actin cytoskeleton in prostate cancer biology.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2021
- Accession Number
- AD1145452
Entities
People
- Michael C. Haffner
Organizations
- Fred Hutchinson Cancer Center