基于PDB文件2grc并利用PyMQL渲染构建蛋白BRG1的三维结构，图片来自维基共享资源。
视黄酸(又称维生素A)和类固醇是在我们身体中发现的激素，它们能够让我们身体免受氧化应激(oxidative stress)带来的伤害，降低炎症，并参与细胞分化过程。肿瘤的特征之一就是它们的细胞丧失分化的能力。因此这些激素拥有阻止癌症发生的较好属性。当前，视黄酸和类固醇也正被人们用来治疗某些类型的白血病。
来自西班牙Bellvitge生物医学研究所(Bellvitge Biomedical Research Institute)的一个研究团队在EMBO Molecular Medicine期刊上发表一篇研究论文，证实BRG1基因缺失导致癌细胞不再对这些激素作出反应，因此肿瘤可能继续生长。
BRG1基因
Montse Sanchez-Cespedes领导的这个来自Bellvitge生物医学研究所的研究团队在几年前发现一个肿瘤抑制基因BRG1在非小细胞肺癌中因发生基因突变而失活。“BRG1蛋白是调节几个基因表达的染色质重塑复合体(chromatin remodelling complex)的一部分”，Montse Sanchez-Cespedes解释道，“而且它与肺部细胞分化相关，允许细胞对某些激素(如维生素A或者类固醇等)作出反应。”
当BRG1基因发生突变而失活时，肿瘤细胞不再对这些激素作出反应，因而它们继续生长和扩散。因为这种原因，这些类型的肿瘤抵抗利用这些激素进行的治疗。
临床应用
Montse Sanchez-Cespedes说，“目前，我们不能恢复病人肿瘤抑制基因BRG1的功能。因此，我们仍然还不能将这一发现应用于临床治疗，但是它使得我们更好地理解肿瘤的生物学特征。在不久的未来，我们将尝试开展的研究就是寻找一些药物试剂来特异性地破坏基因BRG1发生突变的细胞。” (生物谷：towersimper编译)
doi:10.1002/emmm.201200236
PMC:
PMID:
The Tumor Suppressor and Chromatin Remodeling Factor BRG1 Antagonizes Myc Activity and Promotes Cell Differentiation in Human Cancer
Octavio A. Romero, Fernando Setien, Sam John, Pol Gimenez-Xavier, Gonzalo Gómez-López, David Pisano, Enric Condom, Alberto Villanueva, Gordon L. Hager, Montse Sanchez-Cespedes
BRG1, a member of the SWI/SNF complex, is mutated in cancer, but it is unclear how it promotes tumorigenesis. We report that re-expression of BRG1 in lung cancer cells up-regulates lung-specific transcripts, restoring the gene expression signature of normal lung. Using cell lines from several cancer types we found that those lacking BRG1 do not respond to retinoic acid (RA) or glucocorticoids (GC), while restoration of BRG1 restores sensitivity. Conversely, in SH-SY5Y cells, a paradigm of RA-dependent differentiation, abrogation of BRG1 prevented the response to RA. Further, our data suggest an antagonistic functional connection between BRG1 and MYC, whereby refractoriness to RA and GC by BRG1 inactivation involves deregulation of MYC activity. Mechanistically, some of these effects are mediated by BRG1 binding to MYC and MYC-target promoters. The BRG1-MYC antagonism was also evident in primary tumors. Finally, BRG1 restoration significantly dampened invasion and progression and decreased MYC in lung cancer cells orthotopically implanted in nude mice. Thus, BRG1 inactivation enables cancer cells to sustain undifferentiated gene expression programs and prevent its response to environmental stimuli.
