Increased expression but not genetic alteration of BRG1, a component of the SWI/SNF complex, is associated with the advanced stage of human gastric carcinomas

Increased expression but not genetic alteration of BRG1, a component of the SWI/SNF complex, is associated with the advanced stage of human gastric carcinomas
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DOI:
10.1159/000064638
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发表时间:
2001-01-01
期刊:
影响因子:
5
通讯作者:
Yasui, W
Yasui, W
中科院分区:
医学4区
文献类型:
--
作者:
Sentani, K;Oue, N;Yasui, W

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BRG 1是SWI/SNF复合物的一个组成部分,通过染色质重塑调节基因转录。某些人类癌细胞系已显示含有纯合缺失或突变,其中一半集中在外显子4和10,导致BRG 1表达异常。采用实时荧光定量RT-PCR方法检测了38例胃癌组织及相应非肿瘤组织中BRG 1的表达。23例(61%)癌组织中BRG 1的表达高于非肿瘤性粘膜。进展期胃癌(III期和IV期)的T/N比值(肿瘤组织中BRG 1 mRNA相对于相应非肿瘤粘膜中BRG 1 mRNA的表达水平)显著高于I期和II期胃癌(p = 0.029)。此外,有淋巴结转移的胃癌显示出比无转移的胃癌更高水平表达BRG 1的趋势(p = 0.097)。我们还用PCR-SSCP分析了8个胃癌细胞系和33例原发性胃癌中BRG 1基因的遗传变异。在胃癌细胞系和原发性胃癌中均未发现BRG 1基因第4、10和16外显子的SSCP变异。这些结果提示,尽管BRG 1基因异常可能是罕见的,但BRG 1的表达增加可能与胃癌的发生和发展有关。版权所有(C)2002 S. Karger AG,巴塞尔。
BRG1, a component of the SWI/SNF complex, regulates gene transcription through chromatin remodeling. Certain human cancer cell lines have been shown to contain homozygous deletions or mutations, half of which are concentrated in exons 4 and 10, resulting in aberrant BRG1 expression. We examined the expression of BRG1 in 38 gastric carcinomas and corresponding nonneoplastic mucosa by using the quantitative real-time RT-PCR method. Twenty-three carcinomas (61%) showed increased BRG1 expression in tumor tissue in comparison with that in nonneoplastic mucosa. The T/N ratio (the expression level of BRG1 mRNA in tumor tissues relative to those in corresponding nonneoplastic mucosa) in advanced cases of gastric carcinoma (stages III and IV) was significantly higher than that in cases of stage I and II carcinoma (p = 0.029). Furthermore, gastric carcinomas with lymph node metastasis showed a tendency to express BRG1 at a higher level than gastric carcinomas without metastasis (p = 0.097). We also searched for genetic alterations of the BRG1 gene in 8 gastric carcinoma cell lines and 33 primary gastric carcinomas by PCR-SSCP analysis. No SSCP variants in exons 4, 10 and 16 of the BRG1 gene were found in both gastric carcinoma cell lines and primary gastric carcinomas. These results suggest that, although genetic abnormality of BRG1 might be rare, an increased expression of BRG1 might be associated with the development and progression of gastric carcinoma. Copyright (C) 2002 S. Karger AG, Basel.