Role of the tumor suppressor gene Brca1 in genetic stability and mammary gland tumor formation
Role of the tumor suppressor gene Brca1 in genetic stability and mammary gland tumor formation
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DOI：
10.1038/sj.onc.1203269
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发表时间：
2000-02-21
期刊：
影响因子：
8
通讯作者：
Scott, F
中科院分区：
文献类型：
--
作者：
Deng, CX;Scott, F
肿瘤抑制基因BRCA1的胚系突变使女性易患乳腺癌和卵巢癌。目前的证据表明，BRCA1基因的突变并不直接导致肿瘤的形成，而是导致遗传不稳定，使细胞面临高恶性转化的风险。在BRCA1基因突变的动物模型中，BRCA1特定于乳腺上皮细胞，肿瘤发生在长时间潜伏期后低频率的突变腺体中。值得注意的是，引入p53零等位基因显著增强了BRCA1条件突变小鼠的乳腺肿瘤形成。这些结果与BRCA1是一个看守基因的模型是一致的，该基因的缺失会导致遗传不稳定并触发进一步的改变，包括肿瘤抑制基因的失活和/或癌基因的激活，从而导致肿瘤的形成。
Germline mutations in the tumor suppressor BRCA1 predispose women to breast and ovarian cancers. Current evidence demonstrates that mutations in BRCA1 do not directly result in tumor formation, but instead cause genetic instability, subjecting cells to high risks of malignant transformation, In an animal model in which Brca1 is mutated specifically in mammary epithelium, tumorigenesis occurs in mutant glands at low frequency after a long latency. Notably, introduction of a p53-null allele significantly enhanced mammary gland tumor formation in Brca1 conditional mutant mice. These results are consistent with a model that Brca1 is a caretaker gene, whose absence causes genetic instability and triggers further alterations, including inactivation of tumor suppressor genes and/or activation of oncogenes, leading to tumor formation.