Aberrant expression of SWI/SNF catalytic subunits BRG1/BRM is associated with tumor development and increased invasiveness in prostate cancers
doi: 10.1002/pros.20521
pmid: 17075831
Aberrant expression of SWI/SNF catalytic subunits BRG1/BRM is associated with tumor development and increased invasiveness in prostate cancers
AbstractBACKGROUNDBrahma 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.METHODWe 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.RESULTSMicroarray 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.CONCLUSIONSWe 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. Prostate © 2006 Wiley‐Liss, Inc.
- Shaoxing University China (People's Republic of)
- University of Kansas United States
- University of Kansas Medical Center United States
- Shaoxing People's Hospital China (People's Republic of)
- National Center for Chronic Disease Prevention and Health Promotion United States
Male, Chromosomal Proteins, Non-Histone, Gene Expression Profiling, Blotting, Western, DNA Helicases, Nuclear Proteins, Prostatic Neoplasms, Adenocarcinoma, Middle Aged, Immunoenzyme Techniques, Fluorescent Antibody Technique, Direct, Cell Line, Tumor, Biomarkers, Tumor, Humans, Neoplasm Invasiveness, Oligonucleotide Array Sequence Analysis, Transcription Factors
Male, Chromosomal Proteins, Non-Histone, Gene Expression Profiling, Blotting, Western, DNA Helicases, Nuclear Proteins, Prostatic Neoplasms, Adenocarcinoma, Middle Aged, Immunoenzyme Techniques, Fluorescent Antibody Technique, Direct, Cell Line, Tumor, Biomarkers, Tumor, Humans, Neoplasm Invasiveness, Oligonucleotide Array Sequence Analysis, Transcription Factors
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