Synergistic tumor suppressor activity of BRCA2 and p53 in a conditional mouse model for breast cancer
Synergistic tumor suppressor activity of BRCA2 and p53 in a conditional mouse model for breast cancer
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DOI：
10.1038/ng747
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发表时间：
2001-12-01
期刊：
影响因子：
30.8
通讯作者：
Berns, A
中科院分区：
文献类型：
--
作者：
Jonkers, J;Meuwissen, R;Berns, A
一个有缺陷的BRCA2等位基因的遗传使人类患有乳腺癌，以建立与BRCA2相关乳腺癌的小鼠模型，我们在包括乳腺gland上皮的各种上皮组织中产生了有条件性的brca2和/或p53的小鼠条件突变体。尽管在携带有条件BRCA2等位基因的小鼠中没有肿瘤，但在有条件的BRCA2和TRP53等位基因的雌性中频繁出现乳腺和皮肤肿瘤。一个野生型BRCA2等位基因的存在导致肿瘤形成明显延迟。野生型BRCA2等位基因的丧失发生在这些肿瘤的一部分中。我们的结果表明，BRCA2和p53的失活共同介导乳腺肿瘤发生，并表明p53途径的破坏在与BRCA2相关的乳腺癌中至关重要。
Inheritance of one defective BRCA2 allele predisposes humans to breast cancer, To establish a mouse model for BRCA2-associated breast cancer, we generated mouse conditional mutants with BRCA2 and/or p53 inactivated in various epithelial tissues, including mammary-gland epithelium. Although no tumors arose in mice carrying conditional Brca2 alleles, mammary and skin tumors developed frequently in females carrying conditional Brca2 and Trp53 alleles. The presence of one wildtype Brca2 allele resulted in a markedly delayed tumor formation; loss of the wildtype Brca2 allele occurred in a subset of these tumors. Our results show that inactivation of BRCA2 and of p53 combine to mediate mammary tumorigenesis, and indicate that disruption of the p53 pathway is pivotal in BRCA2-associated breast cancer.