Molecular Interactions of Bc1-2 Family Members in Breast Cancer Cells.
Abstract
The treatment of cancer with chemotherapy or radiation therapy is limited by the emergence of tumor cells resistant to these therapies. This resistance limits our ability to successfully treat these neoplasms. A major genetic event that occurs in the genesis and/or progression of cancer is alteration in the pathway of apoptosis. Recent studies indicate that the susceptibility of cancer cells to therapy-induced death is controlled in part by genes that regulate the apoptosis pathway. Of these, bcl-2 and bcl-x are expressed in a wide variety of cancer cells and encode products, bcl-2 and bcl%X%, that repress the apoptotic mechanism. In order to assess the function of bcl-2 and bcl-x in maintaining the survival of cancer cells, an adenoviral vector that expresses bcl-x2, a dominant inhibitor of bcl-2 and bcl-xL constructed. In the absence of exogenous signals, the bcl3-x adenovirus killed cancer cells by apoptosis including primary breast carcinomas. We postulate that apoptotic signals are constitutively expressed in proliferating cancer cells, although repressed by members of the bcl-2 family of proteins. In this proposal, we propose experiments (i) to determine the mechanism involved in bcl-x2-mediated apoptosis of cancer cells using the bcl-x5 adenovirus to dissect molecular interactions of the bcl-2 regulatory pathway and (ii) to characterize cellular proteins that interact with bcl-x3 using biochemical and genetic approached The studies outlined in this proposal should provide novel insight into the apoptosis pathway and lead to alternative therapeutic strategies for the treatment of cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 1999
- Accession Number
- ADA378870
Entities
People
- Gabriel Nunez
Organizations
- University of Michigan