Molecular Analysis of Bcl-xS-Induced Apoptosis in Breast Cancer
Abstract
A major genetic event that occurs in the pathogenesis of breast carcinoma involves alterations in the Bcl-2 survival pathway. In the original proposal, we proposed studies to determine the mechanism involved in Bcl-xS-mediated apoptosis, to characterize cellular proteins that interact with Bcl-xS using biochemical and genetic approaches, and to use a transgenic model of Bcl-xS expression in the breast to assess the requirement for Bcl-2/Bcl-XL in the maintenance of normal breast epithelia and tumor growth. During the last year, we have further studied the apoptotic pathway induced by Bcl-xS. The analysis showed that Bcl-xS kills cells, at least in part, through an Apaf-1-caspase-9 pathway. Bcl-xS associates with Bcl-xL via its BH3 domain and with Apaf-1 possibly through Bcl-xL. We have cloned and characterized a novel Apaf-1 cDNA form that, in contrast to the originally described Apaf-1, activates procaspase-9 in a cytochrome c and dATP-dependent manner. Finally, transgenic mice expressing Bcl-XS in the breast have been crossed with oncogenic erb2-B transgenic mice to assess the effects of Bcl-xS on breast cancer development.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1999
- Accession Number
- ADA372246
Entities
People
- Gabriel Nunez
Organizations
- University of Michigan