生物谷：使用药物有可能会激活一个在癌细胞发育过程中的相关基因，来自密歇根大学（University of Michigan）综合癌症治疗中心的研究报告称。此项发现将有可能借以开发出新型的癌症治疗方法，一种有望治疗多种癌症的方法。
现有的一些较为流行的癌症治疗药物，如Herceptin和Gleevec，主要是针对一些基因突变而引起蛋白过量表达的情况。但是癌症的发生，有时是一些控制细胞生长的基因被关闭引起的。换言之，研究者可以通过运用这些关闭的基因来识别或检测癌症。但是，这方面的研究还是空白。
U-M研究者发现在一些癌细胞中，一个名为Brahma或BRM的基因会发生沉默（不是缺失）。当BRM蛋白接触到一种抑制物后，研究者可以让该基因重新恢复表达。进一步地研究发现，该基因大约在15%的肿瘤中被关闭了，包括肺癌、食道癌、卵巢癌、膀胱癌、结肠癌和乳腺癌，等。
研究者通过使用现有的药物来激活BRM基因，但是，可能新开发的药物将会更加有效。即便如此，研究者们对此项有关癌症治疗领域的发现感到兴奋不已。
“这是‘定向打靶’的，我们可以检测到它的效果。如果我们能开发出效率更高的药物，那么势必会诞生出一类新药。现在，还没有药物是专门针对被关闭的基因的，这是对当前只针对基因过量表达的治疗方法的一个拓展。”此项研究的主持者David Reisman介绍说，他是U-M医学院的内科副教授。
研究文章刊登在在线的Oncogene杂志上，感兴趣的读者可以查阅英文原文。（引自生命经纬）
原始出处:
Oncogene advance online publication 4 June 2007; doi: 10.1038/sj.onc.1210514
The reversible epigenetic silencing of BRM: implications for clinical targeted therapy
S Glaros1, G M Cirrincione1, C Muchardt2, C G Kleer3, C W Michael3 and D Reisman1
1Department of Internal Medicine, Division of Hematology/Oncology, University of Michigan, Ann Arbor, MI, USA
2Expression Génétique et Maladies, URA1644 du CNRS, Département de Biologie du Développement, Institut Pasteur, Bât. Fernbach, Rue du Docteur Roux, Paris Cedex, France
3Department of Pathology, University of Michigan, Ann Arbor, MI, USA
Correspondence: Dr D Reisman, Department of Internal Medicine, Division of Hematology/Oncology, University of Michigan, MRSB2 B570B, Ann Arbor, MI 48103-0686, USA. E-mail: dreisman@umich.edu
Received 21 November 2006; Revised 2 April 2007; Accepted 2 April 2007; Published online 4 June 2007.
The SWI/SNF chromatin-remodeling complex serves as a master switch that directs and limits the execution of specific cellular programs, such as differentiation and growth control. SWI/SNF function requires one of two paralogous ATPase subunits, Brahma (BRM) or BRM-related gene 1 (BRG1), which we previously found are lost together in cancer cell lines and primary lung cancers. Although BRG1 has been found to be mutated in cancer cell lines, the mechanisms underlying BRM silencing are not known. To address this question, we sequenced BRM in 10 BRM/BRG1-deficient cancer cell lines and found that BRM was devoid of abrogating mutations. Moreover, histone deacetylase (HDAC) inhibitors restored BRM expression in each of these BRG1/BRM-deficient cancer cell lines, indicating that epigenetic silencing is a major mechanism underlying the loss of BRM expression. Despite their ability to restore BRM expression, these HDAC inhibitors also blocked BRM function when present. However, after their removal, we observed that BRM expression remained elevated for several days, and during this period, BRM activity was detected. We also found that the suppression of BRM occurs in a broad range of human tumor types and that loss of one or both BRM alleles potentiated tumor development in mice. Thus, BRG1 and BRM are silenced by different mechanisms, and it may be possible to clinically target and reexpress BRM in a number of tumor types, potentially impacting tumor development.
Keywords:
Brahma, Brahma-related gene 1, BRG1/BRM-associated factor, tumor suppressor, lung cancer, SWI/SNF complex
