IR@PKUHSC  > 北京大学基础医学院  > 免疫学系
学科主题基础医学
Genetic and epigenetic control of UNC5C expression in human renal cell carcinoma
Lv, Dan1; Zhao, Wei1; Dong, Dong1; Qian, Xiao-Ping1; Zhang, Yu1; Tian, Xiao-Jun2; Zhang, Jun1
关键词UNC5C Renal cell carcinoma Tumour suppressor DNA methylation Loss of heterozygosity
刊名EUROPEAN JOURNAL OF CANCER
2011-09-01
DOI10.1016/j.ejca.2011.04.021
47期:13页:2068-2076
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]TUMOR-SUPPRESSOR GENE ; CLEAR-CELL ; METHYLATION ANALYSIS ; DNA METHYLATION ; RECEPTORS ; NETRIN-1 ; INACTIVATION ; CANCER ; HYPERMETHYLATION ; PROGRESSION
英文摘要

Inappropriate gene silencing and subsequent promiscuous activity define the transformation of many solid tumours including renal cell carcinoma (RCC). Here, we report that UNC5C, one of the Netrin-1 receptors, was frequently inactivated in RCC cell lines and primary tumours. UNC5C protein was expressed in the proximal convoluted tubules of the human kidney, the presumed origin of clear cell RCC (ccRCC) and papillary RCC (pRCC). Compared to paired adjacent non-malignant tissues, both UNC5C mRNA and protein expression were significantly down-regulated in RCC. Immunohistochemical analysis showed that UNC5C was inactivated in 94.3% of the samples and the loss of UNC5C occurred at the early stage of RCC. Methylation specific PCR showed that UNC5C promoter was methylated in two renal carcinoma cell lines. Pharmacologic demethylation alone or in combination with inhibition of deacetylation dramatically induced UNC5C expression. Furthermore, bisulfite genomic sequencing (BGS) confirmed that dense methylation existed in UNC5C promoter. In paired tumour samples, UNC5C methylation was observed in 12 out of 44 patients (27.3%). Moreover, we analysed the loss of heterozygosity (LOH) of UNC5C in renal cell carcinoma, the LOH was observed in 27 out of 44 patients (61.4%). Finally, restoration of UNC5C expression suppressed the colony formation of renal carcinoma cells. In addition, UNC5C inhibited tumour cell proliferation, migration and enhanced chemosensitivity to cisplatin and etoposide. Therefore, UNC5C acts as a tumour suppressor in RCC and is down-regulated in RCC. Loss of heterozygosity and DNA methylation contribute to the inactivation of UNC5C in renal cell carcinoma. (C) 2011 Elsevier Ltd. All rights reserved.

语种英语
WOS记录号WOS:000295116600018
引用统计
被引频次:14[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
版本出版稿
条目标识符http://ir.bjmu.edu.cn/handle/400002259/54189
专题北京大学基础医学院_免疫学系
北京大学基础医学院
北京大学第三临床医学院_泌尿外科
作者单位1.Peking Univ, Dept Urol, Hosp 3, Beijing 100191, Peoples R China
2.Peking Univ, Dept Immunol, Sch Basic Med Sci, Key Lab Immunol,Minist Hlth,Hlth Sci Ctr, Beijing 100191, Peoples R China
推荐引用方式
GB/T 7714
Lv, Dan,Zhao, Wei,Dong, Dong,et al. Genetic and epigenetic control of UNC5C expression in human renal cell carcinoma[J]. EUROPEAN JOURNAL OF CANCER,2011,47(13):2068-2076.
APA Lv, Dan.,Zhao, Wei.,Dong, Dong.,Qian, Xiao-Ping.,Zhang, Yu.,...&Zhang, Jun.(2011).Genetic and epigenetic control of UNC5C expression in human renal cell carcinoma.EUROPEAN JOURNAL OF CANCER,47(13),2068-2076.
MLA Lv, Dan,et al."Genetic and epigenetic control of UNC5C expression in human renal cell carcinoma".EUROPEAN JOURNAL OF CANCER 47.13(2011):2068-2076.
条目包含的文件
文件名称/大小 文献类型 版本类型 开放类型 使用许可
1-s2.0-S095980491100(1220KB)期刊论文作者接受稿开放获取CC BY-NC-SA浏览 请求全文
个性服务
推荐该条目
保存到收藏夹
查看访问统计
导出为Endnote文件
谷歌学术
谷歌学术中相似的文章
[Lv, Dan]的文章
[Zhao, Wei]的文章
[Dong, Dong]的文章
百度学术
百度学术中相似的文章
[Lv, Dan]的文章
[Zhao, Wei]的文章
[Dong, Dong]的文章
必应学术
必应学术中相似的文章
[Lv, Dan]的文章
[Zhao, Wei]的文章
[Dong, Dong]的文章
相关权益政策
暂无数据
收藏/分享
文件名: 1-s2.0-S0959804911002863-main.pdf
格式: Adobe PDF
所有评论 (0)
暂无评论
 

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。