文章：

SWI/SNF复合物-染色质与癌症

The SWI/SNF complex — chromatin and cancer

原文发布日期：2004-02-01

DOI: 10.1038/nrc1273

类型: Review Article

开放获取: 否

要点：

1. The SWI/SNF complex is an evolutionarily conserved multi-subunit chromatin-remodelling complex, which uses the energy of ATP hydrolysis to mobilize nucleosomes and remodel chromatin, and thereby regulate transcription of target genes.
2. This complex is implicated in cancer development, as several subunits either possess intrinsic tumour-suppressor activity or are required for the activity of other tumour-suppressor genes.
3. SNF5 (also known as INI1), a core subunit of SWI/SNF, is specifically inactivated in malignant rhabdoid tumours, a highly aggressive cancer of early childhood.
4. Whereas homozygous inactivation of Snf5 is embryonic lethal in mice, heterozygous mice are predisposed to develop cancers that readily metastasize and have loss of heterozygosity for Snf5. Inducible inactivation of conditional alleles of Snf5 results in extremely rapid and fully penetrant cancer development.
5. Specific mutations in BRG1 — an ATPase catalytic subunit of the SWI/SNF complex — have been identified in pancreatic, breast, lung and prostate cancer cell lines. Mice that are deficient in Brg1 are embryonic lethal, whereas haploinsufficient mice are predisposed to tumour development at a low incidence.
6. SWI/SNF complexes directly interact with tumour suppressors and oncogenes, such as RB, BRCA1, c-MYC and MLL (mixed-lineage leukaemia).
7. The SWI/SNF complex might also be involved in DNA synthesis, mitotic gene regulation and viral integration. The relationship between these activities and the role of the SWI/SNF complex in cancer development remains to be elucidated.

要点翻译：

1. SWI/SNF复合物是一种进化上保守的多亚基染色质重塑复合物，其利用ATP水解产生的能量驱动核小体位移并重塑染色质结构，从而调控靶基因的转录。
2. 该复合物与癌症发生密切相关，其中多个亚基本身具有抑癌活性或为其他抑癌基因功能所必需。
3. SNF5（亦称INI1）作为SWI/SNF的核心亚基，在恶性横纹肌样瘤（一种高侵袭性的儿童早期肿瘤）中发生特异性失活。
4. 小鼠模型中，Snf5纯合失活会导致胚胎致死，而杂合缺失小鼠则易发生具有高转移倾向的癌症，且肿瘤组织中存在Snf5杂合性缺失。诱导性敲除Snf5条件等位基因可导致极高效率且快速发生的癌症。
5. 在胰腺癌、乳腺癌、肺癌和前列腺癌细胞系中，已发现SWI/SNF复合物的ATP酶催化亚基BRG1存在特定突变。Brg1缺陷小鼠会出现胚胎致死，单倍体不足小鼠则呈现低发率的肿瘤易感性。
6. SWI/SNF复合物可直接与抑癌蛋白及癌蛋白（如RB、BRCA1、c-MYC和MLL混合谱系白血病蛋白）相互作用。
7. 该复合物可能还参与DNA合成、有丝分裂基因调控和病毒整合过程，但这些功能与SWI/SNF在癌症发展中作用的内在联系仍有待阐明。

英文摘要：

The SWI/SNF complex is an evolutionarily conserved multi-subunit chromatin-remodelling complex, which uses the energy of ATP hydrolysis to mobilize nucleosomes and remodel chromatin. Increasing evidence supports a role for this complex in cancer development, as several subunits possess intrinsic tumour-suppressor activity or are required for the activity of other tumour-suppressor genes. For example, conditional inactivation of the Snf5 gene resulted in a highly penetrant cancer phenotype in mice. So, what are the links between the SWI/SNF complex and cancer, and what mechanisms might facilitate its involvement in oncogenesis?

摘要翻译： 

SWI/SNF复合物是一个在进化上保守的多亚基染色质重塑复合物，通过水解ATP提供能量来移动核小体并重塑染色质。越来越多的证据表明该复合物在癌症发展中发挥作用，因为其多个亚基具有内在的抑癌活性，或对其他抑癌基因的活性至关重要。例如，Snf5基因的条件性失活在小鼠中引发了高外显率的癌症表型。那么，SWI/SNF复合物与癌症之间存在哪些联系？又有哪些机制可能促进其在肿瘤发生中的作用？

原文链接：

The SWI/SNF complex — chromatin and cancer