Genetic Susceptibility to Estrogen-Induced Mammary Cancers
Abstract
Estrogens play a central role in the etiology of breast cancer. We have developed the ACI rats as a novel, physiologically relevant, and genetically defined model for the study of breast cancer etiology, treatment and prevention. In this model, estrogens rapidly induce mammary cancers that are estrogen dependent and exhibit aneuploidy. Susceptibility to estrogen-induced mammary cancers behaves as an incompletely dominant trait. Three loci have been identified to date that modify susceptibility in different genetic crosses. In this study we have evaluated allelic imbalances (AI) in a panel of mammary cancers induced by estrogen in female ACI/Copenhagen Fl progeny. Al is common and nonrandom in these cancers. Chromosome 1 exhibited the highest frequency of Al; 34% of examined marker/tumor pairs exhibited Al. Only 5 of 21 tumors did not exhibit Al at one or more marker on chromosome 1. In contrast, the frequency of Al on chromosome 9 was only 0.8%. Al was common on chromosomes 5, 18 and 2, which harbor the Emca1, Emca2 and Emca3 modifiers. These data suggest that non-random Al resulting from LOH and/or gene amplification may play a role in the etiology of estrogen induced mammary cancers.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 01, 2000
- Accession Number
- ADB266385
Entities
People
- James D. Shull
Organizations
- University of Nebraska Medical Center