An epistatic interaction controls the latency of a transgene-induced mammary tumor
An epistatic interaction controls the latency of a transgene-induced mammary tumor
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DOI：
10.1007/s003350010163
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发表时间：
2000-10-01
期刊：
影响因子：
2.5
通讯作者：
Hunter, K
中科院分区：
文献类型：
--
作者：
Le Voyer, T;Lu, ZC;Hunter, K
我们实验室先前的研究表明，在FVB/NJ近交系小鼠背景中，多瘤中T诱导的乳腺肿瘤的潜伏期、肿瘤生长和转移进展可以通过引入不同的遗传背景而显著改变。在这项研究中，我们扩展了这些发现，通过映射一些相互作用的数量性状基因座负责表型的变化。将I/LnJ近交遗传背景引入FVB/NJ-PyMT动物显著加速了原发性肿瘤的出现（出生后35天对57天，p < 10（-7））。建立了回交作图组，并在第15和第9染色体上检测了负责肿瘤加速的基因座。基因型/表型相关性的检查显示，FVB/NJ，而不是I/LnJ等位基因的Chr 15基因座与肿瘤加速，是有条件的存在下，我/LnJ等位基因的Chr 9。这些基因座，命名为Apmt 1和Apmt 2，映射到与人类乳腺癌中的洛缺失相关的同源区域。这些结果表明，这些区域的等位基因变异可能有助于人类乳腺癌的发病年龄。
Previous studies from our laboratory demonstrated that the latency, tumor growth, and metastatic progression of polyoma middle T-induced mammary tumor in an FVB/NJ inbred mouse background could be significantly altered by the introduction of different genetic backgrounds. In this study we extend these findings by mapping a number of interacting quantitative trait loci responsible for the changes in phenotype. Introduction of the I/LnJ inbred genetic background into the FVB/NJ-PyMT animal significantly accelerated the appearance of the primary tumor (35 vs. 57 days postnatal, p < 10(-7)). A backcross mapping panel was established, and loci responsible for the tumor acceleration were detected on Chrs 15 and 9. Examination of the genotype/phenotype correlation revealed that the FVB/NJ but not the I/LnJ allele of the Chr 15 locus was associated with tumor acceleration and was conditional on the presence of I/LnJ allele on Chr 9. These loci, designated Apmt1 and Apmt2, map to homologous regions associated with LOH in human breast cancer. These results suggest that allelic variants of genes in these regions may contribute to age of onset in human breast cancer.