title: BRG1 is a prognostic marker and potential therapeutic target in human breast cancer.
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.
authors.affiliation: Jiangsu Key Laboratory of Biological Cancer Therapy, Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Bai
authors.forename: Pengjin
authors.initials: P
authors.lastname: Mei
authors.forename: Cuipeng
authors.initials: C
authors.lastname: Zhang
authors.forename: Feifei
authors.initials: F
authors.lastname: Chen
authors.forename: Chen
authors.initials: C
authors.lastname: Li
authors.forename: Zhenqiang
authors.initials: Z
authors.lastname: Pan
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.forename: Junnian
authors.initials: J
authors.lastname: Zheng
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D019927:Cyclin E / Q000235:genetics / Q000378:metabolism; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D053208:Kaplan-Meier Estimate; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D019927:Cyclin E; D009687:Nuclear Proteins; D014157:Transcription Factors; D019938:Cyclin D1; C084108:SMARCA4 protein, human; D004265:DNA Helicases