Sun Aijing, Tawfik Ossama, Gayed Bishoy, Thrasher J Brantley, Hoestje Sara, Li Chaoyang, Li Benyi
Department of Pathology, Shaoxing People's Hospital, First Affiliated Hospital of Shaoxing University, Shaoxing, Zhejiang, China.
Prostate. 2007 Feb 1;67(2):203-13. doi: 10.1002/pros.20521.
Brahma gene (BRM) and Brahma-related gene 1 (BRG1) are major components with ATPase enzymatic activities in the nucleosome remodeling SWI/SNF complex, and their expression pattern in human prostate cancers is unknown.
We analyzed a published cDNA microarray data set of prostate cancers for the expression of SWI/SNF genes, and then we evaluated the expression levels of BRG1 and BRM proteins with a semi-quantitative immunohistochemistry (IHC) approach in a pairwise manner of malignant versus benign tissues from individual prostate cancers. The correlation of BRG1/BRM expression with clinical parameters was analyzed.
Microarray data showed an aberrant expression of BRG1 and BRM but not SNF5/INI1 genes in different stages of the disease course. In immunochemistry studies, BRG1 expression was significantly higher in malignant tissues compared to their benign compartments, and this difference was more profound in high-grade cancers. Although BRM expression showed a heterogeneous pattern, the average level of BRM expression was lower in malignant tissues than that in benign tissues. More interestingly, BRG1 and BRM expression showed a reciprocal pattern in both benign and malignant tissues of individual cases. In malignant tissues, higher BRG1 but not BRM expression levels were associated with larger volume of tumor mass. Increased expression of BRG1 but not BRM protein was observed in invasive cancer cells. Consistently, overexpression of exogenous wild-type BRG1 and BRM but not mutant BRG1 enhanced cancer cell invasion in an in vitro cell invasion assay.
We provide the first evidence that aberrant expression of BRG1 and BRM genes is associated with disease development and progression in prostate cancers and increased BRG1 expression may promote tumor growth and invasion.
Brahma基因（BRM）和Brahma相关基因1（BRG1）是核小体重塑SWI/SNF复合物中具有ATP酶活性的主要成分，它们在人类前列腺癌中的表达模式尚不清楚。
我们分析了已发表的前列腺癌cDNA微阵列数据集以了解SWI/SNF基因的表达情况，然后采用半定量免疫组织化学（IHC）方法，以个体前列腺癌的恶性组织与良性组织两两配对的方式评估BRG1和BRM蛋白的表达水平。分析了BRG1/BRM表达与临床参数的相关性。
微阵列数据显示在疾病进程的不同阶段BRG1和BRM基因表达异常，但SNF5/INI1基因无异常表达。在免疫化学研究中，与良性区域相比，恶性组织中BRG1表达显著更高，且这种差异在高级别癌症中更为明显。虽然BRM表达呈现异质性模式，但恶性组织中BRM的平均表达水平低于良性组织。更有趣的是，在个别病例的良性和恶性组织中，BRG1和BRM表达呈现相反模式。在恶性组织中，较高的BRG1表达水平而非BRM表达水平与更大的肿瘤体积相关。在浸润性癌细胞中观察到BRG1蛋白表达增加而非BRM蛋白表达增加。同样，在体外细胞侵袭试验中，外源性野生型BRG1和BRM而非突变型BRG1的过表达增强了癌细胞侵袭。
我们提供了首个证据，表明BRG1和BRM基因的异常表达与前列腺癌的疾病发展和进展相关，且BRG1表达增加可能促进肿瘤生长和侵袭。
