Cooperation of Bcl-XL and c-Myc in Mammary Tumorigenesis
Abstract
Studies of tumor tissue taken from women with breast cancer have demonstrated that the proto-oncogene, c-myc, is more abundant than in normal breast (amplified in 16%, rearranged in 5%, and overexpressed in nearly 70% of all human breast cancers). Similar studies have shown that genes known to influence programmed cell death are also altered in breast tumors. Bcl-x(sub L), known to inhibit apoptosis, is overexpressed in some breast tumors and has been shown to be important in the regulation of apoptosis during mammary gland involution. The pro-apoptotic protein Bax has been demonstrated to be significantly reduced or altogether absent in many breast tumors and has further been shown to cooperate with tumor oncogenes in reducing the protective apoptotic effect early in mammary tumorigenesis. Our bitransgenic mouse studies with constitutive Bcl-x(sub L) expression or loss of Bax in the context of constitutive c-Myc expression have been designed to address whether modulation of c-Myc-induced apoptotic pathways will influence mammary gland development and tumorigenesis. Current data obtained from c-myc/bcl-x(sub L) and bax-knockout/c-myc mice suggest a cooperative role for these apoptosis-modulatory genes with c-Myc in mammary tumorigenesis. 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, 2000
- Accession Number
- ADA395737
Entities
People
- Matthew Jamerson
Organizations
- Georgetown University