Highly penetrant, rapid tumorigenesis through conditional inversion of the tumor suppressor gene Snf5
Highly penetrant, rapid tumorigenesis through conditional inversion of the tumor suppressor gene Snf5
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DOI：
10.1016/s1535-6108(02)00185-x
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发表时间：
2002-11-01
期刊：
影响因子：
50.3
通讯作者：
Orkin, SH
中科院分区：
文献类型：
--
作者：
Roberts, CWM;Leroux, MM;Orkin, SH
最近的数据表明，SWI/SNF染色质重塑复合体也可能作为肿瘤抑制因子。利用一个可逆失活的条件等位基因，我们证明Snf5/Ini1/Baf47/SmarcB1 （SWI/SNF的核心亚基）的缺失导致高渗透的癌症易感，100%的小鼠发展为成熟CD8(+) T细胞淋巴瘤或罕见的横纹肌样肿瘤，中位发病时间仅为11周。值得注意的是，虽然Snf5的缺失易导致侵袭性癌症，但它也是几乎所有非恶性细胞在体内存活所必需的。可逆基因靶向研究证实了Snf5在肿瘤抑制中的关键和特异性作用，为探索Swi/Snf参与肿瘤抑制的遗传途径提供了一个新的系统，并应广泛应用于评估其他重要的肿瘤抑制基因。
Recent data suggest the SWI/SNF chromatin remodeling complex may also act as a tumor suppressor. Utilizing a reversibly inactivating conditional allele, we demonstrate that loss of Snf5/Ini1/Baf47/SmarcB1, a core subunit of SWI/SNF, results in highly penetrant cancer predisposition with 100% of mice developing mature CD8(+) T cell lymphoma or rare rhabdoid tumors with a median onset of only 11 weeks. Notably, while loss of Snf5 predisposes to aggressive cancers, it is also required for survival of virtually all nonmalignant cells in vivo. Reversible gene targeting demonstrates a critical and specific role for Snf5 in tumor suppression, provides a novel system in which to explore the genetic pathways involved in tumor suppression by Swi/Snf, and should be of wide use in evaluating other essential tumor suppressor genes.