Cooperation of Bcl-xL and c-Myc in Mammary Tumorigenesis
Abstract
C-Myc is amplified in 16%, rearranged in 5%, and overexpressed in nearly 70% of all human breast cancers and it regulates both proliferation and apoptosis. BC1-xL, known to inhibit apoptosis potentially by modulating mitochondrial permeability and caspase activation, is overexpressed in some breast tumors and derivative cell lines. Pro-apoptotic Bax has been shown to be significantly reduced or altogether absent in many breast tumors and cell lines. Evidence from c-Myc/TGF-a bitransgenic mice suggests that escape from c-Myc-induced apoptosis may be necessary for continued cell cycle progression and neoplastic development. The focus of this study is the resolution of the role of Bcl-xL overexpression and Bax loss in cooperation with c-Myc overexpression in mammary tumorigenesis; constitutive expression of Bcl-xL and loss of Bax likely disrupt the c-Myc-induce apoptotic pathways without significant alteration in c-Myc-mediated proliferation. c-Myc transgenic/Bax-knockout and c-Myc/Bcl-xL bitransgenic mice have been generated, genotyped, and shall be assessed for altered tumor onset, incidence, growth, and pathological /molecular characteristics once mammary tumors arise. Utilization of these models will aid in the dissection of the role of apoptosis in the development of breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 1999
- Accession Number
- ADA386550
Entities
People
- Matthew H. Jamerson
Organizations
- Georgetown University