1. Cancer Res. 2006 Aug 1;66(15):7793-800.
Genetic bases of estrogen-induced tumorigenesis in the rat: mapping of loci
controlling susceptibility to mammary cancer in a Brown Norway x ACI intercross.
Schaffer BS(1), Lachel CM, Pennington KL, Murrin CR, Strecker TE, Tochacek M,
Gould KA, Meza JL, McComb RD, Shull JD.
Author information:
(1)Department of Genetics, Eppley Institute for Research in Cancer, University of
Nebraska Medical Center, 985805 Nebraska Medical Center, Omaha, NE 68198, USA.
Exposure to estrogens is associated with an increased risk of breast cancer. Our
laboratory has shown that the ACI rat is uniquely susceptible to 17beta-estradiol
(E2)-induced mammary cancer. We previously mapped two loci, Emca1 and Emca2
(estrogen-induced mammary cancer), that act independently to determine
susceptibility to E2-induced mammary cancer in crosses between the susceptible
ACI rat strain and the genetically related, but resistant, Copenhagen (COP) rat
strain. In this study, we evaluate susceptibility to E2-induced mammary cancer in
a cross between the ACI strain and the unrelated Brown Norway (BN) rat strain.
Whereas nearly 100% of the ACI rats developed mammary cancer when treated
continuously with E2, BN rats did not develop palpable mammary cancer during the
196-day course of E2 treatment. Susceptibility to E2-induced mammary cancer
segregated as a dominant or incompletely dominant trait in a cross between BN
females and ACI males. In a population of 251 female (BN x ACI)F(2) rats, we
observed evidence for a total of five genetic determinants of susceptibility. Two
loci, Emca4 and Emca5, were identified when mammary cancer status at sacrifice
was evaluated as the phenotype, and three additional loci, Emca6, Emca7, and
Emca8, were identified when mammary cancer number was evaluated as the phenotype.
A total of three genetic interactions were identified. These data indicate that
susceptibility to E2-induced mammary cancer in the BN x ACI cross behaves as a
complex trait controlled by at least five loci and multiple gene-gene
interactions.
PMID: 16885383 [PubMed - indexed for MEDLINE]
PUBMED: 16885383
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