Mammary-Specific Gene Transfer for Modeling Breast Cancer
Abstract
In order to develop a mouse model system that allows for rapid assessment of genetic lesions involved in breast tumor development, we are adapting a somatic gene transfer system based on avian leukosis virus A (ALV-A) expression vectors and TVA, the receptor for ALV-A. Transgenic mice have been generated that target tv-alpha to the mammary epithelial cells using MMTV and WAP promoters. Mammary epithelial cells from these transgenic mice are susceptible to infection both in vivo and in vitro. Low-grade carcinomas can be induced to progress to higher-grade tumors using viruses that express potent oncogenes. The mouse lines generated will be valuable research tools for gene delivery using the ALV-TVA system. PTEN is a tumor suppressor gene mutated in many neoplasias including breast cancer. It encodes a lipid phosphatase that prevents the activation of Akt. Breeding of a Pten mutant allele into female mice predisposed to mammary oncogenesis, due to transgenic expression of MMTV-Wnt-1, led to more rapid formation of mammary tumors. This finding confirmed the role of Pten in breast tumorigenesis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2001
- Accession Number
- ADA406121
Entities
People
- Harold E. Varmus
- Yi Li
Organizations
- Memorial Sloan Kettering Cancer Center