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Characterization of Genetic Modifiers of Estrogen-Induced Mammary Cancer

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Annual summary rept. 1 Jul 2004-30 Jun 2005

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Prolonged exposure to estrogens is considered a major risk factor for development of breast cancer. When treated with estrogen for 28 weeks, ACI rats develop mammary cancers in over 90 of the population at risk. Genetic crosses between the susceptible ACI rat and resistant Copenhagen COP or Brown Norway BN rats identified a region on chromosome 5 Emca1 that modified the development of estrogen-induced mammary cancer. To define the role of Emca1 in the development of estrogen-induced mammary cancer, a congenic line has been developed ACI.BN-Emca1 in which the resistant BN allele of Emca1 has been introgressed onto an ACI background. Female ACI.BN-Emca1 rats treated with estrogen for 28 weeks exhibit a significant decrease in the incidence of mammary cancer in the population at risk, a significant delay in the latency to the development of mammary cancer, and a significant decrease in the number of tumors per rat compared to ACI rats. These data suggest that Emca1 is a strong modifier of estrogen-induced mammary cancer. Additional congenic sublines, in which the Emca1 locus has been divided into smaller regions, have been generated and will be used to further define the regions on chromosome 5. In addition, microarray analysis of 12 week estrogen-treated mammary tissue from ACI and ACI.BN-Emca1 rats was utilized to identify genes and ESTs that were differentially expressed as a result of estrogen treatment. Analysis of the ACI.BN-Emca1 congenic sublines will be used to more clearly identify the regions on chromosome 5 that modify susceptibility to E2-induced mammary cancer, and microarray analysis will be used to identify genes that are differentially expressed as a result of E2 treatment. These data will provide important information on the mechanisms by which estrogen regulates the development of mammary cancer.

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  • Genetic Engineering and Molecular Biology
  • Medicine and Medical Research

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