Tumor Suppressive Effects of Bromodomain-Containing Protein 7 (BRD7) in Epithelial Ovarian Carcinoma

Abstract

Purpose: Bromodomain-containing protein 7 (BRD7), which is a subunit of SWI/SNF complex, has been recently suggested as a novel tumor suppressor in several cancers. In this study, we investigated the tumor suppressive effect of BRD7 in epithelial ovarian cancer.Experimental Design: We analyzed the expression of BRD7 in human ovarian tissues with real-time PCR. To investigate the functional role of BRD7, we transfected ovarian cancer cells (A2780 and SKOV3) with BRD7 plasmid and checked the cell viability, apoptosis, and invasion. The activities of BRD7 in the signaling pathways associated with carcinogenesis were also tested. In addition, we used the orthotopic mouse model for ovarian cancer to evaluate tumor growth-inhibiting effect by administration of BRD7 plasmid.Results: The BRD7 expression was downregulated in the ovarian cancer tissues compared with normal (P < 0.05), high-grade serous cancer exhibited significantly decreased expression of BRD7 compared with low-grade (P < 0.01) serous cancer. Transfection of BRD7 plasmid to A2780 (p53-wild) or SKOV3 (p53-null) ovarian cancer cells showed the tumor suppressive effects assessed by cell viability, apoptosis, and invasion assay and especially significantly decreased tumor weight in orthotopic mouse model (A2780). Moreover, we found that tumor suppressive effects of BRD7 are independent to the presence of p53 activity in ovarian cancer cells. BRD7 negatively regulated b-catenin pathway, resulting in decreased its accumulation in the nucleus.Conclusions: These results suggested that BRD7 acts as a tumor suppressor in epithelial ovarian cancers independently of p53 activity, via negative regulation of b-catenin pathway. Clin Cancer Res; 20(3); 565-75. Ó2013 AACR.

Integrating ChIP-sequencing and digital gene expression profiling to identify BRD7 downstream genes and construct their regulating network

“…Accumulating evidence demonstrates that inactivation of the BRD7 gene contributes to the development of many human cancers by transcriptional dysregulation [1,2,[6][7][8][9][10][11][12][13]. BRD7 regulates signaling pathways that involve cell growth, apoptosis, cell cycle, and mobility [14][15][16][17][18][19][20][21].…”

“…Accumulating evidence indicates that BRD7 was also down-regulated in multiple types of human cancer, including breast [6], prostate [7], endometrial [8], colorectal [9], ovarian [10], and pancreas cancer [11], glioma [12], and osteosarcoma [13]. BRD7 can inhibit cell growth through multiple mechanisms, including cell cycle arrest and apoptosis [14,15].…”

BRD7 Acts as a Tumor Suppressor Gene in Lung Adenocarcinoma

“…Recent studies demonstrated that BRD7 was mostly located in the nucleus and regulated chromatin remodeling[15–17]. More importantly, increasing evidences showed that BRD7 were downregulated in many cancers such as epithelial ovarian carcinoma, breast cancer, nasopharyngeal cancer and colorectal carcinoma [18–21]. For example, Hu et al showed that BRD7 acted as a tumor suppressor in osteosarcoma, and knockdown of BRD7 increased colony formation, tumor growth and cell proliferation of osteosarcoma[22].…”

“…For example, Hu et al showed that BRD7 acted as a tumor suppressor in osteosarcoma, and knockdown of BRD7 increased colony formation, tumor growth and cell proliferation of osteosarcoma[22]. Park et al demonstrated that overexpression of BRD7 inhibited ovarian cancer cells invasion, apoptosis and viability[18]. However, the role of BRD7 in lung adenocarcinoma is still unknown.…”

The role of microRNA in metastatic processes of non-small cell lung carcinoma

“…akt activation partially blocked mir-410-induced cell proliferation 184 . Brd7 is down-regulated in various malignancies [185][186][187] . However chen and Yu found that Brd7 expression was significantly higher in Nsclc tissues compared to normal lung tissue and also in an Nsclc lymph node metastasis group than that in the non-lymph node metastasis group 188 .…”