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 Thoc 1 protein, which interacts with the N terminal region of Rb protein and therby may mediate some Rb functions. Previous reports show that Thoc1 is unregulated in some cancer types and is required for survival of transformed cells, suggesting Thoc1 is unregulated in some cancer types 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 and delayed development of prostate tumor lesions compared to mice with loss of Rb and p53. Deletion of Thoc1 in cells isolated from the prostate tumors resulted in significant decrease in clonogenicity and loss of viability compared to cells retaining Thoc1 expression. Interestingly, decreased amounts of Thoc1 protein alone in the prostate gland of the mouse did not affect normal prostate gland development. The differential requirement for Thoc1 in tumor cells compared to normal cells suggests that Thoc1 may be a potential target for prostate cancer therapy.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2011
- Accession Number
- ADA548020
Entities
People
- Meenalakshmi Chinnam
Organizations
- Health Research, Incorporated