Genetic determination of susceptibility to estrogen-induced mammary cancer in the ACI rat:: Mapping of Emca1 and Emca2 to chromosomes 5 and 18
Genetic determination of susceptibility to estrogen-induced mammary cancer in the ACI rat:: Mapping of Emca1 and Emca2 to chromosomes 5 and 18
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DOI：
10.1534/genetics.104.033878
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发表时间：
2004-12-01
期刊：
影响因子：
3.3
通讯作者：
Shull, JD
中科院分区：
文献类型：
--
作者：
Gould, KA;Tochacek, M;Shull, JD
荷尔蒙、遗传和环境因素在乳腺癌的复杂病因中扮演主要角色。当持续使用17β-雌二醇(E_2)治疗时，ACI大鼠表现出遗传上易患乳腺癌的倾向。ACI大鼠对E2诱导的乳腺癌的易感性在与抗药性哥本哈根(COP)品系的杂交中似乎分离为不完全显性性状。在(ACI X COP)F-2和(COP X ACI)F-2两个群体中，我们在大鼠5号染色体远端发现了雌激素诱发乳腺癌易感性的主要遗传决定因素。我们的数据与该基因座的ACI等位基因被称为Emca1(雌激素诱导乳腺癌1)的模型最一致。在这些人群中，以不完全显性的方式起作用，既增加了肿瘤的发病率和肿瘤的多样性，也缩短了肿瘤的潜伏期。我们还发现了暗示第二个地点的证据。位于(ACI X COP)F-2群体18号染色体上的Emca2。Emra2的ACI等位基因以显性方式增加发病率和缩短潜伏期。Emca1和Emca2一起独立作用，改变对E2诱导的乳腺癌的易感性。
Hormonal genetic and environmental factors plan major roles in the complex etiology of breast cancer. When treated continuously with 17beta-estradiol (E2) the ACI rat exhibits a genetically conferred propensity to develop mammary cancer. The susceptibility of the ACI rat to E2-induced mammary cancer appears to segregate as an incompletely dominant trait in crosses to the resistant Copenhagen (COP) strain. In both (ACI X COP)F-2 and (COP X ACI)F-2 populations, we find strong evidence fora major genetic determinant of susceptibility to E2-induced mammary cancer on distal rat chromosome 5. Our data are most consistent with a model in which the ACI allele of this locus, termed Emca1 (estrogen-induced mammary cancer 1). acts in an incompletely dominant manner to increase both tumor incidence and tumor multiplicity as well as to reduce tumor latency in these populations. We also find evidence suggestive of a Second locus. Emca2, on chromosome 18 in the (ACI X COP)F-2 population. The ACI allele of Emra2 acts in a dominant manner to increase incidence and decrease latency. Together, Emca1 and Emca2 act independently to modify susceptibility to E2-induced mammary cancer.