Scaffold attachment factors SAFB1 and SAFB2: Innocent bystanders or critical players in breast tumorigenesis?
Scaffold attachment factors SAFB1 and SAFB2: Innocent bystanders or critical players in breast tumorigenesis?
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DOI：
10.1002/jcb.10685
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发表时间：
2003-11-01
影响因子：
4
通讯作者：
Oesterreich, S
中科院分区：
文献类型：
--
作者：
Oesterreich, S
支架附着因子B1（SAFB 1）和SAFB 2是大的多功能蛋白质，其涉及许多细胞过程，包括染色质组织、转录调控、RNA剪接和应激反应。虽然这两个同源蛋白质显示出高度相似性，并且功能结构域高度保守，但有证据表明它们也具有独特的性质。例如，SAFB 2可以在细胞核和细胞质中发现，而SAFB 1似乎主要定位在细胞核中。在乳腺癌细胞中，SAFB作为雌激素受体辅阻遏物和生长抑制剂发挥作用。SAFB蛋白表达在大约20%的乳腺癌中丢失。有趣的是，这两个基因位于染色体19 p13上，非常接近，头对头定向，这是一个在临床乳腺癌标本中经常丢失的基因座。此外，在乳腺肿瘤中发现了SAFB 1突变，而在邻近的正常组织中不存在。SAFB 1和SAFB 2是新的乳腺肿瘤抑制基因的可能性，以及它们如何发挥这一作用，进行了讨论。(C)2003 Wiley-Liss，Inc.
Scaffold attachment factor B1 (SAFB1) and SAFB2 are large, multifunctional proteins that have been implicated in numerous cellular processes including chromatin organization, transcriptional regulation, RNA splicing, and stress response. While the two homologous proteins show high similarity, and functional domains are highly conserved, evidence suggests that they also have unique properties. For example, SAFB2 can be found in both the nucleus and cytoplasm, whereas SAFB1 seems to be mainly localized in the nucleus. In breast cancer cells, SAFBs function as estrogen receptor corepressors and growth inhibitors. SAFB protein expression is lost in approximately 20% of breast cancers. Interestingly, the two genes reside in close proximity, oriented head-to-head, on chromosome 19p13, a locus which is frequently lost in clinical breast cancer specimens. Furthermore, SAFB1 mutations have been identified in breast tumors that were not present in adjacent normal tissue. The possibility that SAFB1 and SAFB2 are novel breast tumor suppressor genes, and how they might function in this role, are discussed. (C) 2003 Wiley-Liss, Inc.