DID YOU KNOW? DTIC has over 3.5 million final reports on DoD funded research, development, test, and evaluation activities available to our registered users. Click
HERE to register or log in.
Accession Number:
ADA355313
Title:
Molecular Analysis of Bcl-xs-Induced Apoptosis in Breast Cancer.
Descriptive Note:
Annual rept. 1 Jul 97-30 Jun 98
Corporate Author:
MICHIGAN UNIV ANN ARBOR SCHOOL OF MEDICINE
Report Date:
1998-07-01
Pagination or Media Count:
19.0
Abstract:
A major genetic event that occurs in the pathogenesis of breast carcinoma involves alterations in the Bcl-2 survival pathway. To determine the role of the Bcl-2 family in maintaining cancer cell viability, we constructed a recombinant adenovirus vector that expresses Bcl-xs, a dominant inhibitor of these proteins. 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-2Bcl-xL in the maintenance of normal breast epithelia and tumor growth. During the last two years, we have characterized the interaction of Bcl-xs with Bcl-2 and Bcl-xL and identified through a genetic screen, HRK, a novel protein that interacts with Bcl-2 and Bcl-xL. Mutational analysis of Bcl-xs revealed a conserved region of this protein that is important for interaction with Bcl-xL and induction of apoptosis. Bcl-xL and Bcl-xs were found to associate with Apaf-1, a critical regulator of caspases and cell death, suggesting that Bcl-xs might antagonize Bcl-xL through Apaf-1. Finally, transgenic mice expressing Bcl-xs in the breast have been developed and partially characterized.
Distribution Statement:
APPROVED FOR PUBLIC RELEASE
