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学科主题: 基础医学
题名:
PTEN C-Terminal Deletion Causes Genomic Instability and Tumor Development
作者: Sun, Zhuo1,2; Huang, Chuanxin2; He, Jinxue2; Lamb, Kristy L.2; Kang, Xi1,2; Gu, Tingting2; Shen, Wen Hong2; Yin, Yuxin1,2
刊名: CELL REPORTS
发表日期: 2014-03-01
DOI: 10.1016/j.celrep.2014.01.030
卷: 6, 期:5, 页:844-854
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Cell Biology
研究领域[WOS]: Cell Biology
关键词[WOS]: EPITHELIAL-MESENCHYMAL TRANSITION ; COMMON FRAGILE SITES ; COWDEN-SYNDROME ; SUPPRESSOR GENE ; CANCER ; MICE ; MUTATIONS ; BREAST ; FHIT ; ACTIVATION
英文摘要:

Tumor suppressor PTEN controls genomic stability and inhibits tumorigenesis. The N-terminal phosphatase domain of PTEN antagonizes the PI3K/AKT pathway, but its C-terminal function is less defined. Here, we describe a knockin mouse model of a nonsense mutation that results in the deletion of the entire Pten C-terminal region, referred to as Pten DC. Mice heterozygous for Pten DC develop multiple spontaneous tumors, including cancers and B cell lymphoma. Heterozygous deletion of the Pten C-terminal domain also causes genomic instability and common fragile site rearrangement. We found that Pten C-terminal disruption induces p53 and its downstream targets. Simultaneous depletion of p53 promotes metastasis without influencing the initiation of tumors, suggesting that p53 mainly suppresses tumor progression. Our data highlight the essential role of the PTEN C terminus in the maintenance of genomic stability and suppression of tumorigenesis.

语种: 英语
所属项目编号: CA133008 ; GM100478 ; 2010CB912202 ; 30930021 ; 5100003
项目资助者: NIH ; China National Major Scientific Program ; National Natural Science Foundation of China ; Beijing Natural Science Foundation ; Shu Fan Education and Research Foundation
WOS记录号: WOS:000333037800009
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/53128
Appears in Collections:基础医学院_期刊论文

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作者单位: 1.Peking Univ, Hlth Sci Ctr, Sch Basic Med Sci, Inst Syst Biomed,Dept Pathol, Beijing 100191, Peoples R China
2.Cornell Univ, Weill Med Coll, Dept Radiat Oncol, New York, NY 10065 USA

Recommended Citation:
Sun, Zhuo,Huang, Chuanxin,He, Jinxue,et al. PTEN C-Terminal Deletion Causes Genomic Instability and Tumor Development[J]. CELL REPORTS,2014,6(5):844-854.
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