99: A Novel Myc-Interacting Protein with Features of a Breast Tumor Suppressor Gene Product.
Abstract
Bin1 is a novel tumor suppressor that interacts with and inhibits the oncogenic properties of Myc, which is widely activated in breast cancer. Last year, we generated Bin1 monoclonal antibodies, cloned the human Bin1 gene and promoter, and showed that Bin1 is expressed in normal breast epithelial cells but very frequently missing in malignant breast tumor cell lines. This year, we performed an immunohistochemical study confirming loss of Bin1 in approx. 50% of a panel of 20 primary breast tumors. Loss of Bin1 was not correlated with other markers tested, supporting utility as a novel and potentially informative marker. Gene deletion did not explain loss of expression. A methylation-specific PCR assay was developed to examine methylation and possible downregulation of the CpG-rich Bin1 promoter. We generated an inducible adenoviral vector system to use for biological tests and showed that Bin1 inhibits growth by apoposis. Deletion analysis identified a key effector domain of Bin1. We cloned the murine Bin1 gene and initiated a gene knockout' project. In related work, we showed that Bin1 is required for Myc-mediated apoptosis but also for differentiation of cells containing normal Myc, suggesting why Bin1 may lost so often in various tumors including breast tumors.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 1998
- Accession Number
- ADA368439
Entities
People
- George Prendergast
Organizations
- University of Pennsylvania