Heterogeneous SWI/SNF chromatin remodeling complexes promote expression of microphthalmia-associated transcription factor target genes in melanoma.
Heterogeneous SWI/SNF chromatin remodeling complexes promote expression of microphthalmia-associated transcription factor target genes in melanoma.
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DOI：
10.1038/onc.2009.304
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发表时间：
2010-01-07
期刊：
影响因子：
8
通讯作者：
de la Serna, I. L.
中科院分区：
文献类型：
--
作者：
Keenen, B.;Qi, H.;Saladi, S. V.;Yeung, M.;de la Serna, I. L.
小眼球相关转录因子(MITF)促进黑素细胞分化和细胞周期停滞。矛盾的是，MITF还促进黑色素瘤的存活和增殖，就像一个世系生存癌基因一样。因此，了解调节黑色素瘤细胞MITF活性的机制至关重要。SWI/SNF染色质重塑酶是由两个相关的ATPase之一BRG1或BRM和9-12相关因子(BAFs)组成的多蛋白复合体。我们先前确定BRG1与MITF相互作用以促进黑素细胞分化。然而，目前尚不清楚SWI/SNF酶是否调控不同类别的MITF靶基因在黑色素瘤中的表达。在这项研究中，我们研究了黑色素瘤细胞中SWI/SNF亚单位的表达，观察到BRG1或BRM的下调，但没有伴随着这两种ATPase的丢失。在BRG1缺失的SK-MEL5细胞中重新导入BRG1可增强分化特异性MITF靶基因的表达和对顺铂的耐药性。在SK-MEL5细胞中，单个ATPase BRM的下调抑制了分化特异性和促增殖的MITF靶基因的表达，并在体外抑制了肿瘤的形成。我们的数据表明，由BRG1或BRM亚单位组成的异质SWI/SNF复合体促进不同和重叠的MITF靶基因的表达，并且至少需要一个ATPase才能使黑色素瘤发生。
The microphthalmia-associated transcription factor (MITF) promotes melanocyte differentiation and cell cycle arrest. Paradoxically, MITF also promotes melanoma survival and proliferation, acting like a lineage survival oncogene. Thus, it is critically important to understand the mechanisms that regulate MITF activity in melanoma cells. SWI/SNF chromatin remodeling enzymes are multiprotein complexes composed of one of two related ATPases, BRG1 or BRM, and 9-12 associated factors (BAFs). We previously determined that BRG1 interacts with MITF to promote melanocyte differentiation. However, it was unclear whether SWI/SNF enzymes regulate the expression of different classes of MITF target genes in melanoma. In this study, we characterized SWI/SNF subunit expression in melanoma cells and observed down-regulation of BRG1 or BRM, but not concomitant loss of both ATPases. Re-introduction of BRG1 in BRG1 deficient SK-MEL5 cells enhanced expression of differentiation specific MITF target genes and resistance to cisplatin. Down-regulation of the single ATPase, BRM, in SK-MEL5 cells inhibited expression of both differentiation specific and pro-proliferative MITF target genes and inhibited tumorigenicity in vitro. Our data suggest that heterogeneous SWI/SNF complexes composed of either the BRG1 or BRM subunit promote expression of distinct and overlapping MITF target genes and that at least one ATPase is required for melanoma tumorigenicity.
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影响因子：
10.5
作者：
Kadam, S;McAlpine, GS;Emerson, BM
通讯作者：
Emerson, BM
DOI：
10.1073/pnas.0600213103
发表时间：
2006-06-27
影响因子：
11.1
作者：
Chen, Kevin G.;Valencia, Julio C.;Gottesman, Michael M.
通讯作者：
Gottesman, Michael M.
DOI：
10.1111/j.1600-0749.1995.tb00679.x
发表时间：
1995-12-01
期刊：
PIGMENT CELL RESEARCH
影响因子：
--
作者：
Eberle, J;Garbe, C;Orfanos, CE
通讯作者：
Orfanos, CE
影响因子：
5.3
作者：
De la Serna, IL;Carlson, KA;Imbalzano, AN
通讯作者：
Imbalzano, AN
影响因子：
7.8
作者：
Bandyopadhyay D;Curry JL;Lin Q;Richards HW;Chen D;Hornsby PJ;Timchenko NA;Medrano EE
通讯作者：
Medrano EE