Roberts Charles W M, Leroux Monique M, Fleming Mark D, Orkin Stuart H
Division of Hematology-Oncology, Dana-Farber Cancer Institute and Children's Hospital, Department of Pediatrics, Harvard Medical School and Howard Hughes Medical Institute, Boston, MA 02115, USA.
Cancer Cell. 2002 Nov;2(5):415-25. doi: 10.1016/s1535-6108(02)00185-x.
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.
近期数据表明，SWI/SNF染色质重塑复合体可能也发挥着肿瘤抑制因子的作用。利用一个可逆转失活的条件性等位基因，我们证明，SWI/SNF的核心亚基Snf5/Ini1/Baf47/SmarcB1缺失会导致癌症易感性显著增加，100%的小鼠会发生成熟的CD8(+) T细胞淋巴瘤或罕见的横纹肌样瘤，中位发病时间仅为11周。值得注意的是，虽然Snf5缺失易引发侵袭性癌症，但它也是体内几乎所有非恶性细胞存活所必需的。可逆基因靶向技术证明了Snf5在肿瘤抑制中的关键且特定的作用，提供了一个新系统来探索Swi/Snf参与肿瘤抑制的遗传途径，并且在评估其他重要的肿瘤抑制基因方面应具有广泛用途。
