BRD4 as a therapeutic target for nonfunctioning and growth hormone pituitary adenoma
文献类型：期刊论文
| 作者 | Shi, Chengzhang2,3,4,5; Ye, Zhao2,3,4,5; Han, Jie13; Ye, Xiaoqing13,14; Lu, Wenchao13; Ji, Chenxing2,3,4,5; Li, Zizhou13; Ma, Zengyi2,3,4,5; Zhang, Qilin2,3,4,5; Zhang, Yichao2,3,4,5,6,7,8 |
| 刊名 | NEURO-ONCOLOGY
 |
| 出版日期 | 2020-04-04 |
| 卷号 | 22期号:8页码:1114-1125 |
| ISSN号 | 1522-8517 |
| DOI | 10.1093/neuonc/noaa084 |
| 文献子类 | Article |
| 英文摘要 | Background. Nonfunctioning pituitary adenoma (NFPA) and growth hormone pituitary adenoma (GHPA) are major subtypes of pituitary adenomas (PAs). The primary treatment is surgical resection. However, radical excision remains challenging, and few effective medical therapies are available. It is urgent to find novel targets for the treatment. Bromodomain-containing protein 4 (BRD4) is an epigenetic regulator that leads to aberrant transcriptional activation of oncogenes. Herein, we investigated the pathological role of BRD4 and evaluated the effectiveness of BRD4 inhibitors in the treatment of NFPA and GHPA. Methods. The expression of BRD4 was detected in NFPA, GHPA, and normal pituitary tissues. The efficacies of BRD4 inhibitors were evaluated in GH3 and MMQ cell lines, patient-derived tumor cells, and in vivo mouse xenograft models of PA. Standard western blots, real-time PCR, and flow cytometry experiments were performed to investigate the effect of BRD4 inhibitors on cell cycle progression, apoptosis, and the expression patterns of downstream genes. Results. Immunohistochemistry studies demonstrated the overexpression of BRD4 in NFPA and GHPA. In vitro and in vivo studies showed that treatment with the BRD4 inhibitor ZBC-260 significantly inhibited the proliferation of PA cells. Further mechanistic studies revealed that ZBC-260 could downregulate the expression of c-Myc, B-cell lymphoma 2 (Bea and related genes, which are vital factors in pituitary tumorigenesis. Conclusion. In this study, we determined the overexpression of BRD4 in NFPA and GHPA and assessed the effects of BRD4 inhibitors on PA cells in vitro and in vivo. Our findings suggest that BRD4 is a promising therapeutic target for NFPA and GHPA. |
| WOS关键词 | C-MYC ; EXPRESSION ; INHIBITION ; MANAGEMENT ; PROLIFERATION ; DIAGNOSIS ; BINDING |
| WOS研究方向 | Oncology ; Neurosciences & Neurology |
| 语种 | 英语 |
| 出版者 | OXFORD UNIV PRESS INC |
| WOS记录号 | WOS:000593120100009 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/309411]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Ding, Hong; Zhao, Yao |
| 作者单位 | 1.China Pharmaceut Univ, Dept Med Chem, Nanjing, Peoples R China; 2.Fudan Univ, Huashan Hosp, Shanghai Med Coll, Dept Neurosurg, 958 Jin Guang Rd, Shanghai, Peoples R China; 3.Fudan Univ, Neurosurg Inst, Shanghai, Peoples R China; 4.Shanghai Clin Med Ctr Neurosurg, Shanghai, Peoples R China; 5.Shanghai Pituitary Tumor Ctr, Shanghai, Peoples R China; 6.Fudan Univ, State Key Lab Med Neurobiol, Inst Brain Sci, Shanghai, Peoples R China; 7.Fudan Univ, MOE Frontiers Ctr Brain Sci, Inst Brain Sci, Shanghai, Peoples R China; 8.Fudan Univ, Huashan Hosp, Natl Clin Res Ctr Aging & Med, Shanghai, Peoples R China; 9.Fudan Univ, Huashan Hosp, Shanghai Med Coll, Dept Endocrinol, Shanghai, Peoples R China; 10.Fudan Univ, Huashan Hosp, Shanghai Med Coll, Dept Pathol, Shanghai, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Shi, Chengzhang,Ye, Zhao,Han, Jie,et al. BRD4 as a therapeutic target for nonfunctioning and growth hormone pituitary adenoma[J]. NEURO-ONCOLOGY,2020,22(8):1114-1125. |
| APA | Shi, Chengzhang.,Ye, Zhao.,Han, Jie.,Ye, Xiaoqing.,Lu, Wenchao.,...&Zhao, Yao.(2020).BRD4 as a therapeutic target for nonfunctioning and growth hormone pituitary adenoma.NEURO-ONCOLOGY,22(8),1114-1125. |
| MLA | Shi, Chengzhang,et al."BRD4 as a therapeutic target for nonfunctioning and growth hormone pituitary adenoma".NEURO-ONCOLOGY 22.8(2020):1114-1125. |
入库方式： OAI收割
来源：上海药物研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。