Functional Interaction Between Rb and Thoc1 in Mouse Prostate Tumorigenesis
Abstract
A large percentage of prostate cancers show either loss or mutational inactivation of the Rb tumor suppressor gene. Rb mediates its tumor suppressor function through its association with other cellular proteins. Our study focuses on Thoc1 protein, which interacts with the N terminal region of Rb and thereby may mediate some Rb functions. Previous reports show that Thoc1 is upregulated in breast and lung cancers and is required for survival of transformed cells, suggesting Thoc1 may play a role in tumorigenesis. To test our hypothesis, we are using a mouse model of prostate cancer where prostate-specific deletion of Rb and p53 genes leads to development of metastatic adenocarcinoma. We find that deletion of Thoc1, Rb and p53 genes leads to increased survival of mice compared to mice with loss of Rb and p53. Histopathological analyses of prostate tissue revealed that Thoc1 is required at early stages of prostate tumorigenesis. Additional studies are underway, which will enable us to understand mechanisms of Thoc1 action in prostate tumorigenesis. Our preliminary findings and previous reports showing differential requirement for Thoc1 in tumor cells compared to normal cells suggests that Thoc1 may be a potential target for therapy of prostate cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2010
- Accession Number
- ADA534931
Entities
People
- Meenalakshmi Chinnam
Organizations
- Health Research, Incorporated