BRG1 expression is increased in human cutaneous melanoma
BRG1 expression is increased in human cutaneous melanoma
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DOI：
10.1111/j.1365-2133.2010.09851.x
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发表时间：
2010-09-01
影响因子：
10.3
通讯作者：
Li, G.
中科院分区：
文献类型：
--
作者：
Lin, H.;Wong, R. P. C.;Li, G.
研究背景SWI/SNF染色质重塑复合物在细胞分化、细胞周期调控和DNA修复等细胞过程中起重要作用。SWI/SNF亚基的异常表达参与癌症的发展。SWI/SNF复合物的核心亚基SNF 5已被证明在恶性横纹肌样肿瘤中失活，并被定义为肿瘤抑制因子。然而，催化亚基BRG 1在癌症中的作用尚未明确。ObjectivesTo研究BRG 1在黑色素瘤发展中的作用，我们检测了BRG 1在不同阶段黑色素细胞病变中的表达，并分析了BRG 1表达与临床病理变量和患者生存率之间的相关性。原发性黑色素瘤90例，转移性黑色素瘤47例。结果BRG 1在原发性黑色素瘤和转移性黑色素瘤中的表达均高于异型增生痣（P <0.0 0 1），而在恶性黑色素瘤中BRG 1的表达明显高于异型增生痣（P < 0.0 0 1）。我们没有发现BRG 1表达与黑色素瘤患者生存率之间存在任何相关性。此外，我们证明了在黑色素瘤细胞系中敲低BRG 1导致细胞增殖能力显著降低。这种减少的细胞增殖是由于G（1）期阻滞作为细胞周期蛋白D（1）下调后BRG 1 knockdown.ConclusionsOur数据表明，BRG 1是显着增加，在人类黑色素瘤，并参与黑色素瘤的启动。
P>BackgroundThe SWI/SNF chromatin remodelling complex plays important roles in cellular processes including cell differentiation, cell cycle control and DNA repair. Aberrant expression of SWI/SNF subunits is involved in cancer development. The core subunit of the SWI/SNF complex, SNF5, has been shown to be inactivated in malignant rhabdoid tumours and has been defined as a tumour suppressor. However, the role of the catalytic subunit, BRG1, is not well defined in cancer.ObjectivesTo investigate the role of BRG1 in melanoma development, we examined the expression of BRG1 in melanocytic lesions at different stages and analysed the correlation between BRG1 expression and clinicopathological variables and patient survival.MethodsUsing tissue microarray and immunohistochemistry, we evaluated BRG1 staining in 48 dysplastic naevi, 90 primary melanomas and 47 metastatic melanomas. We studied melanoma cell proliferative ability with reduced BRG1 expression by small interfering RNA using cell proliferation assay and cell cycle analysis.ResultsWe found that BRG1 expression was increased in primary melanoma and metastatic melanoma compared with dysplastic naevi (P < 0 center dot 0001). We did not find any correlation between BRG1 expression and melanoma patient survival. In addition, we demonstrated that knockdown of BRG1 in melanoma cell lines resulted in significantly reduced cell proliferative ability. This reduced cell proliferation is due to G(1) phase arrest as cyclin D(1) is downregulated upon BRG1 knockdown.ConclusionsOur data indicate that BRG1 is significantly increased in human melanoma and is involved in melanoma initiation.