Nkx3.1 controls the DNA repair response in the mouse prostate

被引:11
作者
Zhang, Hailan [1 ]
Zheng, Tian [1 ,2 ]
Chua, Chee Wai [1 ,3 ]
Shen, Michael [1 ,3 ]
Gelmann, Edward P. [1 ]
机构
[1] Columbia Univ, Med Ctr, Dept Pathol & Med, Herbert Irving Comprehens Canc Ctr, 177 Ft Washington Ave,MHB 6N-435, New York, NY 10032 USA
[2] Columbia Univ, Med Ctr, Dept Stat, Herbert Irving Comprehens Canc Ctr, New York, NY 10032 USA
[3] Columbia Univ, Med Ctr, Dept Dev & Cell Biol, Herbert Irving Comprehens Canc Ctr, New York, NY 10032 USA
关键词
NKX3; 1; DNA repair; haploinsufficiency; histone; 2AX; INTRAEPITHELIAL NEOPLASIA; TOPOISOMERASE-I; CANCER; GENE; EXPRESSION; ANDROGEN; DAMAGE; DELETION; ADENOCARCINOMA; CARCINOMA;
D O I
10.1002/pros.23131
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
BACKGROUNDThe human prostate tumor suppressor NKX3.1 mediates the DNA repair response and interacts with the androgen receptor to assure faithful completion of transcription thereby protecting against TMPRSS2-ERG gene fusion. To determine directly the effect of Nkx3.1 in vivo we studied the DNA repair response in prostates of mice with targeted deletion of Nkx3.1. METHODSUsing both drug-induced DNA damage and -irradiation, we assayed expression of -histone 2AX at time points up to 24hr after induction of DNA damage. RESULTSWe demonstrated that expression of Nkx3.1 influenced both the timing and magnitude of the DNA damage response in the prostate. CONCLUSIONSNkx3.1 affects the DNA damage response in the murine prostate and is haploinsufficient for this phenotype. Prostate 76:402-408, 2016. (c) 2015 The Authors. The Prostate published by Wiley Periodicals, Inc.
引用
收藏
页码:402 / 408
页数:7
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