Genetic Susceptibility to Estrogen-Induced Mammary Cancers
Abstract
Our laboratory has played a leading role in establishing the female ACI rat as a physiologically relevant animal model for the study of breast cancer etiology. We were the first to demonstrate that the naturally occurring estrogen, 17-beta-estradiol (E2), induces rapid development of mammary cancers in the female ACI rat (1). We have demonstrated that the unique susceptibility of the ACI rat to E2-induced mammary cancers is inherited in ACI x Copenhagen (COP) and ACI x Brown Norway (BN) genetic crosses as a complex dominant trait (2), and most recently have mapped three genetic loci that confer and/or modulate susceptibility to E2-induced mammary cancers (3). In this USAMRMC flinded research we are testing the hypothesis that genomic instability, specifically loss of heterozygosity (LOR), is an important contributing factor in the etiology of E2-induced mammary cancers. The primary experimental approach is to utilize a battery of polymorphic genetic loci to assess LOH in mammary tumors induced by E2 in ACI/COP Fl and ACI/BN Fl rats. To date, we have demonstrated that E2-induced mammary cancers exhibit genomic instability. Assays for detecting LOR have been established. Preliminary data indicate that LOR occurs within regions of the rat genome demonstrated by us to contain gene(s) that confer and/or modulate susceptibility to E2-induced mammary cancers.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 01, 1999
- Accession Number
- ADB262490
Entities
People
- James Shull
Organizations
- University of Nebraska Omaha