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学科主题: 临床医学
题名:
Testicular orphan nuclear receptor 4-associated protein 16 promotes non-small cell lung carcinoma by activating estrogen receptor beta and blocking testicular orphan nuclear receptor 2
作者: Fang, Fang1; Zheng, Qingfeng1; Zhang, Jianzhi1; Dong, Bin2; Zhu, Sainan4; Huang, Xiaoyun1; Wang, Yang1; Zhao, Bingtian1; Li, Shaolei1; Xiong, Hongchao1; Chen, Jinfeng1; Wu, Nan1; Song, Sonya Wei3; Chang, Chawnshang5,6,7,8; Yang, Yue1
关键词: ER beta ; testicular orphan nuclear receptor 2 ; TR4-associated protein 16 ; non-small cell lung cancer
刊名: ONCOLOGY REPORTS
发表日期: 2013
DOI: 10.3892/or.2012.2107
卷: 29, 期:1, 页:297-305
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Oncology
研究领域[WOS]: Oncology
关键词[WOS]: CANCER ; EXPRESSION ; SUPERFAMILY ; ALPHA ; TRANSACTIVATION ; TRANSCRIPTION ; SUPPRESSION ; SURVIVAL ; THERAPY ; TISSUE
英文摘要:

The possible involvement of estrogen receptors (ERs) and testicular orphan nuclear receptors (TRs) in human non-small cell lung carcinoma (NSCLC) has been suggested, but their precise roles and their relationship remain largely unknown. This study aimed to investigate whether TR4-associated protein 16 (TRA16) regulates the ER beta and TR2 pathways and could be a potential target in NSCLC. We used tissue microarrays including NSCLC tissues (n=154) and negative controls (n=14) to examine the expression of TRA16 and ER beta, and in vitro reporter gene assays, the mammalian two-hybrid method and immunoprecipitation in Cos-1 cells to investigate the relationships among TRA16, ER beta and TR2. We found that TRA16 was highly expressed in approximately 90% of the NSCLC tissues examined. TRA16 overexpression was significantly associated with TNM stage, tumor size, lymph node metastasis, tumor thrombus in vein, tumor differentiation and prognosis of NSCLC patients, in which TRA16 was shown to be an independent prognostic factor. Introduction of TRA16 into Cos-1 cells enhanced cell proliferation. Co-expression of TRA16 and ER beta in Cos-1 cells using different reporter gene systems and mammalian two-hybrid approaches revealed that TRA16 enhanced ER beta-mediated transcriptional activity. By adopting similar approaches, and immunoprecipitation and immunocyto-fluorescence assays, we found that TRA16 also interacted with TR2, and blocked the TR2 inhibitory effect on ER beta. Our findings demonstrate that TRA16 could be a promising diagnostic and prognostic biomarker in NSCLC, and promotes cancer cell growth through activation of the ER beta pathway by interacting with ER beta and TR2.

语种: 英语
所属项目编号: DK56784
项目资助者: National Institutes of Health ; Beijing Natural Science Foundation ; National Natural Science Foundation
WOS记录号: WOS:000312183900041
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/57390
Appears in Collections:北京大学临床肿瘤学院_临床实验室_期刊论文

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作者单位: 1.Peking Univ, Canc Hosp & Inst, Minist Educ, Dept Thorac Surg 2,Key Lab Carcinogenesis & Trans, Beijing 100142, Peoples R China
2.Peking Univ, Canc Hosp & Inst, Minist Educ, Dept Pathol,Key Lab Carcinogenesis & Translat Res, Beijing 100142, Peoples R China
3.Peking Univ, Canc Hosp & Inst, Minist Educ, Clin Res Lab, Beijing 100142, Peoples R China
4.Peking Univ, Hosp 1, Dept Med Stat, Beijing 100034, Peoples R China
5.Univ Rochester, Med Ctr, Dept Pathol, Rochester, NY 14642 USA
6.Univ Rochester, Med Ctr, Dept Urol, Rochester, NY 14642 USA
7.Univ Rochester, Med Ctr, Dept Radiat Oncol, Rochester, NY 14642 USA
8.Univ Rochester, Med Ctr, Ctr Canc, George Whipple Lab Canc Res, Rochester, NY 14642 USA

Recommended Citation:
Fang, Fang,Zheng, Qingfeng,Zhang, Jianzhi,et al. Testicular orphan nuclear receptor 4-associated protein 16 promotes non-small cell lung carcinoma by activating estrogen receptor beta and blocking testicular orphan nuclear receptor 2[J]. ONCOLOGY REPORTS,2013,29(1):297-305.
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