Decristofaro M F, Betz B L, Rorie C J, Reisman D N, Wang W, Weissman B E
Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill 27599, USA.
J Cell Physiol. 2001 Jan;186(1):136-45. doi: 10.1002/1097-4652(200101)186:1<136::AID-JCP1010>3.0.CO;2-4.
Organization of genomic DNA into chromatin aids in the regulation of gene expression by limiting access to transcriptional machinery. The SWI/SNF family of complexes, which are conserved from yeast to humans, are ATP-dependent chromatin-remodeling enzymes required for the transcription of a number of genes in yeast. In humans, the gene encoding the BAF47/hSNF5 subunit of the complex, located at 22q11.2, has been found to be mutated in a number of human tumors including rhabdoid, rhabdomyosarcoma, chronic myeloid leukemia, and CNS tumors such as medulloblastomas and choroid plexus carcinomas. In addition, loss of heterozygosity (LOH) has been reported for the BAF47 region in breast and liver cancer. LOH has also been reported in breast and ovarian cancer within 17q12-25, a gene-rich area including BRCA1, BAF60B, and BAF57. Interestingly, the gene encoding the BAF155/hSWI3 subunit of the complex maps to 3p21-p23, an area of chromosomal deletion seen in a number of human adenocarcinomas including breast, kidney, pancreas, and ovary. To look for abnormalities in these proteins as well as the SWI/SNF complex in general, we have determined the protein status of core human SWI/SNF components BAF170, BAF155, BAF57, BAF53a, and BAF47 in 21 breast cell lines. The complex status in other human tumor cell lines of various tissue types was also examined. We also determined the protein status of the human SWI2 homologues, hBRM/SWI2alpha and BRG1/SWI2beta as well as two other proteins found in human SWI/SNF complexes, BAF180 and BAF250. In this study, we identified the first cell line negative for the BAF57 protein as well as a pancreatic carcinoma cell line negative for both the BRG-1 and hBRM proteins.
基因组DNA组装成染色质通过限制转录机制的可及性来辅助基因表达的调控。从酵母到人类都保守存在的SWI/SNF复合物家族，是酵母中许多基因转录所需的依赖ATP的染色质重塑酶。在人类中，位于22q11.2的该复合物的BAF47/hSNF5亚基的编码基因，已发现在多种人类肿瘤中发生突变，包括横纹肌样瘤、横纹肌肉瘤、慢性粒细胞白血病以及中枢神经系统肿瘤如髓母细胞瘤和脉络丛癌。此外，已报道在乳腺癌和肝癌中BAF47区域存在杂合性缺失（LOH）。在17q12 - 25（一个包含BRCA1、BAF60B和BAF57的基因丰富区域）的乳腺癌和卵巢癌中也报道了LOH。有趣的是，该复合物的BAF155/hSWI3亚基的编码基因定位于3p21 - p23，这是在包括乳腺癌、肾癌、胰腺癌和卵巢癌在内的多种人类腺癌中可见染色体缺失的区域。为了寻找这些蛋白质以及一般SWI/SNF复合物中的异常情况，我们测定了21种乳腺癌细胞系中人类SWI/SNF核心成分BAF170、BAF155、BAF57、BAF53a和BAF47的蛋白质状态。还检测了其他各种组织类型的人类肿瘤细胞系中的复合物状态。我们还测定了人类SWI2同源物hBRM/SWI2α和BRG1/SWI2β以及在人类SWI/SNF复合物中发现的另外两种蛋白质BAF180和BAF250的蛋白质状态。在本研究中，我们鉴定出第一个BAF57蛋白阴性的细胞系以及一个BRG - 1和hBRM蛋白均阴性的胰腺癌细胞系。
