|The Tumor-Suppressive Function of UNC5D and Its Repressed Expression in Renal Cell Carcinoma|
|Pang, Xue-Wen1; Lu, Dan1; Dong, Dong1; Zhou, Yu1; Lu, Min2; Li, Yan1; Tian, Xiao-Jun3; Zhang, Yu1; Zhang, Jun1|
|刊名||CLINICAL CANCER RESEARCH|
|WOS标题词||Science & Technology|
|关键词[WOS]||EPIGENETIC INACTIVATION ; CANCER SUSCEPTIBILITY ; DEPENDENCE RECEPTORS ; NETRIN-1 RECEPTOR ; BLADDER-CANCER ; BREAST-CANCER ; KIDNEY CANCER ; GROWTH-FACTOR ; LUNG-CANCER ; SFRP GENES|
Purpose: As a newly added member of the UNC5H receptors, the function of UNC5D/H4 in tumorigenesis remains poorly defined. The aim of this study was to examine the expression of UNC5D in primary renal cell carcinomas (RCC), analyze the mechanisms responsible for its downregulation in RCC, and assess its functional relevance to tumor growth and migration.
Experimental Design: Forty-four paired primary RCCs and corresponding adjacent noncancerous tissues were collected. The mRNA and protein expression level of UNC5D was assessed by reverse transcriptase-PCR, real-time PCR, or immunohistochemistry. Epigenetic alterations in UNC5D promoter and LOH in the UNC5D locus were also analyzed. Ectopic expression of UNC5D in renal cancer cells with silenced expression of UNC5D was used for analysis of the biologic functions of UNC5D.
Results: UNC5D expression was attenuated in multiple carcinoma cell lines including renal cancer cells. Similar reduction was also observed in primary RCC tissues as compared with paired adjacent noncancerous tissues. Methylation-specific PCR showed hypermethylation in UNC5D promoter in a significant proportion (18 of 44) of tumor tissue (40.9%). LOH of UNC5D was observed in 13 of 44 patients with RCCs (29.5%). Restoration of UNC5D expression in renal cancer cells significantly inhibited cell proliferation, anchorage-dependent and -independent growth, as well as migration and invasion, whereas knockdown of UNC5D promoted cell growth. Furthermore, ectopic expression of UNC5D induced G(2)-M cell-cycle arrest.
Conclusions: UNC5D is a functional tumor suppressor that is frequently downregulated in RCCs due to promoter hypermethylation and LOH. (c) 2013 AACR.
|项目编号||2011CB946103 ; 7122104 ; 81072395|
|资助机构||National Basic Research Program of China ; Beijing Municipal Natural Science Foundation ; National Natural Science Foundation of China|
|作者单位||1.Peking Univ, Hlth Sci Ctr, Dept Pathol, Sch Basic Med Sci, Beijing 100191, Peoples R China|
2.Peking Univ, Hlth Sci Ctr, Dept Immunol, Key Lab Med Immunol,Minist Hlth, Beijing 100191, Peoples R China
3.Peking Univ, Hosp 3, Dept Urol, Beijing 100191, Peoples R China
|Pang, Xue-Wen,Lu, Dan,Dong, Dong,et al. The Tumor-Suppressive Function of UNC5D and Its Repressed Expression in Renal Cell Carcinoma[J]. CLINICAL CANCER RESEARCH,2013,19(11):2883-2892.|
|APA||Pang, Xue-Wen.,Lu, Dan.,Dong, Dong.,Zhou, Yu.,Lu, Min.,...&Zhang, Jun.(2013).The Tumor-Suppressive Function of UNC5D and Its Repressed Expression in Renal Cell Carcinoma.CLINICAL CANCER RESEARCH,19(11),2883-2892.|
|MLA||Pang, Xue-Wen,et al."The Tumor-Suppressive Function of UNC5D and Its Repressed Expression in Renal Cell Carcinoma".CLINICAL CANCER RESEARCH 19.11(2013):2883-2892.|
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