Genetic Susceptibility to Estrogen-Induced Mammary Cancers
Abstract
Estrogens & important in the etiology of breast cancer. We have developed the ACI rat as a novel, physiologically relevant, and genetically defined model for the study of breast cancer etiology, treatment and prevention. In this model, estrogens induce mammary cancers that are estrogen dependent and aneuploid. Susceptibility to estrogen-induced mammary cancers behaves as an incompletely dominant trait. Three loci have been identified that modify susceptibility in different genetic crosses of the ACI female with either the Copenhagen (COP) or Brown Norway (BN) male rat. We evaluated allelic imbalances (AI) among 21 chromosomes in estrogen-induced mammary cancers from female (ACI x COP) F1 progeny. AI is common and widespread in these cancers. Chromosomes 1, 5, 7, 17, 18 and to a lesser extent chromosome 11, contained significant nonrandom AI. In contrast, no AI was observed on chromosome 9. AI was common on chromosomes 5, 18 and 2, which harbor the Emca1, Emca2 and Emca3 modifiers. Preliminary evaluation of AI on chromosomes 1, 5,9, 18 in tumors from the (ACI x BN)F1 also reveals widespread instability. These data suggest that non-random AI 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, 2001
- Accession Number
- ADB282181
Entities
People
- James D. Shull
Organizations
- University of Nebraska Medical Center