Cooperation of Bc1-XL and c-Myc in Mammary Tumorigenesis.
Abstract
C-Myc oncogene has been reported to be amplified in 25-30% and overexpressed in more than 70% of human breast cancers and has been demonstrated to be involved in signaling cell proliferation and apoptosis. The Bcl-xL protein, a member of the Bcl-2 apoptosis- modulatory family, is known to block apoptotic cell death under a wide variety of conditions and has been shown to be overexpressed in some human breast cancers and breast cancer cell lines. Evidence from a c-Myc/TGFalpha bitransgenic mouse model 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 to determine if Bcl-xL expression cooperates with c-Myc overexpression in mammary tumorigenesis in vi and in vitro by blocking c-Myc-induced apoptosis but not c-Myc-mediated cell cycle progression and cell proliferation. Transgenic c-Myc mice will be mated with transgenic Bcl-xL mice to produce bitransgenic offspring which will be observed to determine whether Bcl-xL expression is sufficient to synergize with c-Myc and enhance mammary tumor incidence and accelerate tumor onset (latency). The utilization of this model system will aid in the dissection of the molecular mechanisms behind the development of breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 1998
- Accession Number
- ADA363615
Entities
People
- Matthew H. Jamerson
Organizations
- Georgetown University