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Neurogenin 3-Directed Cre Deletion of Tsc1 Gene Causes Pancreatic Acinar Carcinoma
Ding, Li1; Han, Lingling1; Li, Yin1; Zhao, Jing1; He, Ping2; Zhang, Weizhen1,3
刊名NEOPLASIA
2014-11-01
DOI10.1016/j.neo.2014.08.010
16期:11页:909-917
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Oncology
研究领域[WOS]Oncology
关键词[WOS]TRANSGENIC MICE ; CELL-CARCINOMA ; NEUROENDOCRINE TUMORS ; CANCER DEVELOPMENT ; IN-VIVO ; MTOR ; RAPAMYCIN ; DIFFERENTIATION ; EXPRESSION ; ENDOCRINE
英文摘要

The role of tuberous sclerosis complex (TSC) in the pathogenesis of pancreatic cancers remains largely unknown. The present study shows that neurogenin 3 directed Cre deletion of Tsc1 gene induces the development of pancreatic acinar carcinoma. By cross-breeding the Neurog3-cre mice with Tsc1(loxp/loxp) mice, we generated the Neurog3-Tsc1-/- transgenic mice in which Tsc1 gene is deleted and mTOR signaling activated in the pancreatic progenitor cells. All Neurog3-Tsc1-/- mice developed notable adenocarcinoma-like lesions in pancreas starting from the age of 100 days old. The tumor lesions are composed of cells with morphological and molecular resemblance to acinar cells. Metastasis of neoplasm to liver and lung was detected in 5% of animals. Inhibition of mTOR signaling by rapamycin significantly attenuated the growth of the neoplasm. Relapse of the neoplasm occurred within 14 days upon cessation of rapamycin treatment. Our studies indicate that activation of mTOR signaling in the pancreatic progenitor cells may trigger the development of acinar carcinoma. Thus, mTOR may serve as a potential target for treatment of pancreatic acinar carcinoma.

语种英语
WOS记录号WOS:000345516900003
项目编号81030012 ; 81330010 ; 81390354 ; 1-13-BS-225
资助机构National Institutes of Health (NIH) ; National Natural Science Foundation of China ; American Diabetes Association
引用统计
被引频次:6[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/64833
专题北京大学第三临床医学院_超声诊断科
北京大学基础医学院
北京大学第三临床医学院_超声影像科
作者单位1.Peking Univ, Hlth Sci Ctr, Dept Physiol & Pathophysiol, Beijing 100191, Peoples R China
2.Peking Univ, Hosp 3, Dept Ultrasound, Beijing 100191, Peoples R China
3.Univ Michigan, Med Ctr, Dept Surg, Ann Arbor, MI 48109 USA
推荐引用方式
GB/T 7714
Ding, Li,Han, Lingling,Li, Yin,et al. Neurogenin 3-Directed Cre Deletion of Tsc1 Gene Causes Pancreatic Acinar Carcinoma[J]. NEOPLASIA,2014,16(11):909-917.
APA Ding, Li,Han, Lingling,Li, Yin,Zhao, Jing,He, Ping,&Zhang, Weizhen.(2014).Neurogenin 3-Directed Cre Deletion of Tsc1 Gene Causes Pancreatic Acinar Carcinoma.NEOPLASIA,16(11),909-917.
MLA Ding, Li,et al."Neurogenin 3-Directed Cre Deletion of Tsc1 Gene Causes Pancreatic Acinar Carcinoma".NEOPLASIA 16.11(2014):909-917.
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