BRG1 Is a Prognostic Marker and Potential Therapeutic Target in Human Breast Cancer |
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| Authors: | Jin Bai Pengjin Mei Cuipeng Zhang Feifei Chen Chen Li Zhenqiang Pan Hui Liu Junnian Zheng |
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| Institution: | 1. Jiangsu Key Laboratory of Biological Cancer Therapy, Xuzhou Medical College, Xuzhou, Jiangsu, China.; 2. The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.; 3. School of Pathology, Xuzhou Medical College, Xuzhou, Jiangsu, China.; 4. Department of Oncological Sciences, Mount Sinai School of Medicine, New York, New York, United States of America.; University of Bonn, Institut of Experimental Hematology and Transfusion Medicine, Germany, |
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| Abstract: | BRG1, a core component of the SWI/SNF chromatin-remodeling complex, has been implicated in cancer development; however, the biological significance of BRG1 in breast cancer remains unknown. We explored the role of BRG1 in human breast cancer pathogenesis. Using tissue microarray and immunohistochemistry, we evaluated BRG1 staining in 437 breast cancer specimens and investigated its role in breast cancer cell proliferation, migration and invasion. Our Kaplan-Meier survival curves showed that high BRG1 expression is inversely correlated with both overall (P = 0.000) and disease-specific (P = 0.000) 5-year patient survival. Furthermore, we found that knockdown of BRG1 by RNA interference markedly inhibits cell proliferation and causes cessation of cell cycle. This reduced cell proliferation is due to G1 phase arrest as cyclin D1 and cyclin E are diminished whereas p27 is upregulated. Moreover, BRG1 depletion induces the expression of TIMP-2 but reduces MMP-2, thereby inhibiting the ability of cells to migrate and to invade. These results highlight the importance of BRG1 in breast cancer pathogenesis and BRG1 may serve as a prognostic marker as well as a potentially selective therapeutic target. |
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