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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

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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
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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®

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27 引用的参考文献

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最近 180 天: 2

2013 年至今: 11

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目录： Current Contents Connect®