Tumor Suppressive Effects of Bromodomain-Containing Protein 7 (BRD7) in Epithelial Ovarian Carcinoma
Tumor Suppressive Effects of Bromodomain-Containing Protein 7 (BRD7) in Epithelial Ovarian Carcinoma
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DOI：
10.1158/1078-0432.ccr-13-1271
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发表时间：
2014-02-01
影响因子：
11.5
通讯作者：
Bae, Duk-Soo
中科院分区：
文献类型：
--
作者：
Park, Young-Ae;Lee, Jeong-Won;Bae, Duk-Soo
用途：含溴结构域蛋白7（BRD 7）是SWI/SNF复合物的一个亚基，最近被认为是多种癌症的新型肿瘤抑制因子。在本研究中，我们研究了BRD 7在上皮性卵巢癌中的肿瘤抑制作用。实验设计：我们分析了BRD 7在人卵巢组织中的表达，用实时荧光PCR。为了研究BRD 7的功能作用，我们用BRD 7质粒转染卵巢癌细胞（A2780和SKOV 3），并检查细胞活力、凋亡和侵袭。还测试了BRD 7在与致癌相关的信号通路中的活性。结果：BRD 7在卵巢癌组织中的表达明显低于正常卵巢组织（P < 0.05），高级别浆液性卵巢癌组织中BRD 7的表达明显低于低级别浆液性卵巢癌组织（P < 0.01）。BRD 7质粒转染到A2780（p53-野生型）或SKOV 3（p53-无效型）卵巢癌细胞中显示出通过细胞活力、凋亡和侵袭测定评估的肿瘤抑制作用，尤其是在原位小鼠模型（A2780）中显著降低肿瘤重量。此外，我们发现BRD 7的肿瘤抑制作用与卵巢癌细胞中p53活性的存在无关。BRD 7负调控β-catenin通路，导致其在细胞核中的积累减少。结论：这些结果表明，BRD 7通过负调控β-catenin通路，独立于p53活性，在上皮性卵巢癌中发挥肿瘤抑制作用。(C)2013年AACR。
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 beta-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 beta-catenin pathway. (C) 2013 AACR.