Development of Spontaneous Mammary Tumors in BALB/c-p53+/-Mice: Detection of Early Genetic Alterations and the Mapping of BALB/c Susceptibility Genes
Abstract
The TP53 tumor suppressor gene is defective in the majority of sporadic breast cancers, and breast cancer is the most frequent tumor type in women with Li-Fraumeni syndrome and bear germline mutations in TP53. We have used BALB/c-Trp53+/- mice as a model of Li- Fraumeni syndrome to follow the pathogenic changes in mammary glands of BALB/c-Trp53+/- mice and map genes that can alter sensitivity to mammary tumors. Normal mammary tissues from BALB/c-Trp53+/- mice did not reveal gross karyotypic instability or gross hyperproliferative changes. Hyperplastic tissues and intraepithelial neoplasias retained the wild type allele of Trp53 and expressed estrogen receptors. However, transition to invasive lesions was accompanied by a loss of the wild type allele of Trp53 and loss of estrogen receptor. Though BALB/c-Trp53+/- mice develop spontaneous mammary tumors, C57BL/6-Trp53+/- mice are resistant. A genome pan has identified a low-penetrance modifier locus on mouse chromosome 7. Fine mapping of the region of interest is being undertaken.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2004
- Accession Number
- ADA424523
Entities
People
- Joseph Jerry
- Sallie Smith
Organizations
- University of Massachusetts Amherst