The ACI Rat as a Genetically Defined Animal Model for the Study of Estrogen Induced Mammary Cancers
We have demonstrated that physiologic levels of 17β-estradiol (E2) rapidly induce mammary cancer development in ovary intact, but not ovariectomized, female ACI rats. Susceptibility to E2 induced mammary cancers in F1, F2 and backcross (BC) progeny from a genetic cross between the highly susceptible ACI strain and the highly resistant Copenhagen (COP) rat strain, has now been examined. Susceptibility in progeny from a cross between the ACI strain and a second highly resistant rat strain, Brown Norway (BN), is currently being evaluated. Data from these genetic studies strongly suggest that the unique susceptibility of the ACI rat strain to development of E2 induced mammary cancers is conferred by a limited number of genes, making mapping and eventual cloning of these genes experimentally tractable. The phenotypically defined F2 and BC progeny are being used in linkage studies to identify the genetic loci that confer and/or modulate susceptibility to E2 induced mammary cancers. Data accumulated to date indicate that: 1) the genetic etiology of estrogen induced mammary cancers in the ACI rat is distinct from that of dimethylbenz-a- anthracene induced mammary cancers; and 2) the rat homologs of the known human breast cancer susceptibility genes BRCA1 and BRCA2 do not confer susceptibility to estrogen induced mammary cancer in the ACI rat strain.
KeywordsBreast Cancer Mammary Carcinoma Mammary Cancer Brown Norway Complex Genetic Trait
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