Tumor Suppressor Mechanism in Breast Cancer: Studies in Genetically Engineered Mice
Abstract
The p53 and pRb tumor suppressor pathways are frequently altered in human breast cancer. Although animal models have begun to explore mechanisms for these proteins, the roles can be different depending on the cancer type. Our previous studies in a mouse brain epithelial tumor model have demonstrated the importance of pRb in tumor initiation and of p53 in tumor progression, and have established p53-dependent apoptosis as a means of tumor suppression. In this model, brain cells are induced to proliferate aberrantly by tissue-specific expression of T(sup 121), a small T antigen oncoprotein that inactivates pRb. This causes slow growing, but highly apoptotic tumors. Further inactivation of p53 causes a dramatic decline in cell death and rapid acceleration of tumor growth. We propose similar studies to examine the pRb and p53 roles in breast cancer. The full T antigen oncoprotein (inactivates both pRb and p53) has been shown to induce mammary tumors in transgenic mice. Here, the T(sup 121) oncoprotein will be tissue-specifically expressed in mammary epithelium by mammary-specific promoters to test the role of pRb. Further analysis using knock out strains will address the role of p53. Such preclinical models are essential for progress in breast cancer research.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2001
- Accession Number
- ADA398943
Entities
People
- Terry A. Van Dyke
Organizations
- University of North Carolina at Chapel Hill