Tumorigenesis in mice carrying a truncating Brca1 mutation
Tumorigenesis in mice carrying a truncating Brca1 mutation
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DOI：
10.1101/gad.879201
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发表时间：
2001-05-15
影响因子：
10.5
通讯作者：
Efstratiadis, A
中科院分区：
文献类型：
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作者：
Ludwig, T;Fisher, P;Efstratiadis, A
我们产生了小鼠突变体携带的Brca 1基因座的修改（Brca 1（tr）），消除了C-末端的一半的蛋白质产品，并获得的结果表明，根据遗传背景，失踪的BRCT和/或其他领域是生存的，但对肿瘤抑制必不可少的。大多数明显的亚纯型Brca 1（TR/TR）突变体发展成各种肿瘤。淋巴瘤在所有年龄段都被检测到，而肉瘤和癌症，包括乳腺癌，在很长的潜伏期后才出现。乳腺肿瘤的组织病理学模式显示出惊人的变异性，这表明在其进展中随机参与致瘤途径，其中Brca 1（tr/tr）突变显然是一个晚期参与者。
We generated mouse mutants carrying in the Brca1 locus a modification (Brca1(tr)) that eliminates the C-terminal half of the protein product and obtained results indicating that, depending on genetic background, the missing BRCT and/or other domains are dispensable for survival, but essential for tumor suppression. Most of the apparently hypomorphic Brca1(tr/tr) mutants developed various tumors. Lymphomas were detected at all ages, whereas sarcomas and carcinomas, including breast cancer, appeared after a long latency. The mammary tumors showed striking variability in histopathological patterns suggesting stochastic engagement of tumorigenic pathways in their progression, to which the Brca1(tr/tr) mutation was apparently a late participant.