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| Folliculin deficient renal cancer cells show higher radiosensitivity through autophagic cell death |
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Folliculin Deficient Renal Cancer Cells Show Higher Radiosensitivity through Autophagic Cell Death 作者:Zhang, Q (Zhang, Qi)[ 1,2 ] ; Si, SH (Si, Shuhui)[ 2 ] ; Schoen, S (Schoen, Sue)[ 2 ] ; Jin, XB (Jin, Xun-Bo)[ 1 ] ; Chen, JD (Chen, Jindong)[ 2 ] ; Wu, G (Wu, Guan)[ 2,3,4 ] JOURNAL OF UROLOGY 卷: 191 期: 6 页: 1880-1888 DOI: 10.1016/j.juro.2014.01.001 出版年: JUN 2014 查看期刊信息 JOURNAL OF UROLOGY 出版商 ELSEVIER SCIENCE INC, 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA ISSN: 0022-5347 eISSN: 1527-3792 研究领域 Urology & Nephrology 摘要 Purpose: Mutations in the FLCN gene are responsible for fibrofolliculoma, pulmonary and renal cysts, and renal cell carcinoma in patients with Birt-Hogg-Dube syndrome. To explore therapeutic approaches to renal cell carcinoma in patients with Birt-Hogg-Dube syndrome we investigated the anticancer effects of irradiation on folliculin deficient renal cancer cells. Materials and Methods: Folliculin deficient (UOK257 and ACHN-5968) and folliculin expressing (UOK257-2 and ACHN-sc) cell lines were used in this study. Clonogenic assays were used to determine the radiosensitivity of folliculin deficient and expressing renal cell carcinoma cells. Apoptosis was detected in these cells by DAPI and TUNEL assays after irradiation. Monodansylcadaverine analysis, GFP-LC3 assay and Western blot were performed to monitor the autophagic process. Results: Folliculin deficient cells were more sensitive to irradiation than their folliculin expressing counterparts. The enhanced effects of irradiation on folliculin deficient cells were mediated by increased autophagy but not by apoptosis. An increased Beclin 1 protein level and an activated mitogen-activated protein kinase pathway were identified as the key regulators of increased autophagy in these folliculin deficient cells. Inhibiting autophagy with 3-methyladenine or beclin 1 siRNA obviously increased radioresistance in folliculin deficient cells. Moreover, irradiation combined with autophagic inducer rapamycin significantly increased autophagy and radiosensitivity in folliculin deficient renal cell carcinoma cells. Conclusions: Findings suggest that folliculin deficient renal cell carcinoma cells are highly sensitive to irradiation due to increased autophagic cell death, unlike other types of renal cell carcinoma. Irradiation plus autophagy inducers, eg rapamycin, might be a potentially more effective therapeutic approach to folliculin deficient renal cell carcinoma. 关键词 作者关键词:kidney; carcinoma; renal cell; Birt-Hogg-Dube syndrome; estrone; autophagy KeyWords Plus:HOGG-DUBE-SYNDROME; MALIGNANT GLIOMA-CELLS; PROSTATE-CANCER; INDUCTION; CARCINOMA; APOPTOSIS; INHIBITION; PATHWAY; PROTEIN; TUMORS 作者信息 通讯作者地址: Chen, JD (通讯作者) Univ Rochester, Med Ctr, Dept Urol, 601 Elmwood Ave,Box 656, Rochester, NY 14642 USA. 增强组织信息的名称 University of Rochester 地址: [ 1 ] Shandong Univ, Prov Hosp, Minimally Invas Urol Ctr, Jinan 250100, Peoples R China 增强组织信息的名称 Shandong University [ 2 ] Univ Rochester, Med Ctr, Dept Urol, Rochester, NY 14642 USA 增强组织信息的名称 University of Rochester [ 3 ] Univ Rochester, Med Ctr, Dept Pathol, Rochester, NY 14642 USA 增强组织信息的名称 University of Rochester [ 4 ] Univ Rochester, Med Ctr, Wilmot Canc Ctr, Rochester, NY 14642 USA 增强组织信息的名称 University of Rochester 电子邮件地址:jindong_chen@urmc.rochester.edu; guan_wu@urmc.rochester.edu 基金资助致谢 基金资助机构 授权号 Department of Urology, University of Rochester Medical Center 查看基金资助信息关闭基金资助信息 Supported by the Department of Urology, University of Rochester Medical Center. 出版商 ELSEVIER SCIENCE INC, 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA 类别 / 分类 研究方向:Urology & Nephrology Web of Science 类别:Urology & Nephrology 文献信息 文献类型:Article 语种:English 入藏号: WOS:000336531100100 PubMed ID: 24434776 ISSN: 0022-5347 eISSN: 1527-3792 期刊信息 目录： Current Contents Connect® 其他信息 IDS 号: AI0IS Web of Science 核心合集中的 "引用的参考文献": 27 Web of Science 核心合集中的 "被引频次": 0 影响因子 4.36 4.064 2014 5 年 JCR® 类别 类别中的排序 JCR 分区 UROLOGY & NEPHROLOGY 10/78 Q1 数据来自第 2014 版 Journal Citation Reports® 引文网络 0 被引频次 27 引用的参考文献 查看 Related Records 查看引证关系图 创建引文跟踪 (数据来自 Web of ScienceTM 核心合集) 全部被引频次计数 0 / 所有数据库 0 / Web of Science 核心合集 0 / BIOSIS Citation Index 0 / 中国科学引文数据库 0 / Data Citation Index 0 / Russian Science Citation Index 0 / SciELO Citation Index 使用次数 最近 180 天: 2 2013 年至今: 11 进一步了解 此记录来自: Web of ScienceTM 核心合集 在其他数据库中查看记录: 查看 最新数据 (在 Current Contents Connect® 中) 查看 生物学数据 (在 BIOSIS Citation IndexSM 中) 建议修正 如果希望提高此记录中数据的质量，请提供修正建议。 期刊信息 目录： Current Contents Connect® |
2楼2016-05-09 12:57:12