Identification of Two Candidate Tumor Suppressor Genes on Chromosome l7p13.3: Assessment of their Roles in Breast and Ovarian Carcinogenesis
Abstract
OVCA1, is a candidate tumor suppressor gene, which maps to a region of frequent allelic loss in breast and ovarian cancer at 1 7p13.3. OVCA1 is mutated in some tumor cell lines, and its protein levels are decreased or lost in nearly 40% of breast and ovarian adenocarcinomas. Expression of low levels of exogenous OVCA1 results in dramatic growth suppression and decreased levels of cyclin Dl. OVCA1 codes for a highly conserved protein with no known function but the C-terminal region of OVCAl interacts with an RNA binding motif protein, named RBM8A. We have recently found that OVCAl exists in at least two forms: a 48 kDa and a 50-kDa protein. 2-D gel western blotting revealed that OVCA1 is extensively modified post-translationally in tumor cells leading to a dramatic shift in p1. These aberrant modifications result in the p50OVCA1 form and loss of immunoreactive p48OVCA1. Studies of the molecular mechanisms regulating OVCA1 expression and localization, and its interaction with RBM8A are continuing. Overall, our studies indicate that altered expression and/or post-translational modifications of OVCAl is associated with the development of breast and ovarian tumors and suggest a potentially new mechanism for the inactivation of tumor suppressors in cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2000
- Accession Number
- ADA383954
Entities
People
- Andrew K. Godwin
Organizations
- Fox Chase Cancer Center