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学科主题: 临床医学
题名:
Neurogenin 3-Directed Cre Deletion of Tsc1 Gene Causes Pancreatic Acinar Carcinoma
作者: Ding, Li1; Han, Lingling1; Li, Yin1; Zhao, Jing1; He, Ping2; Zhang, Weizhen1,3
刊名: NEOPLASIA
发表日期: 2014-11-01
DOI: 10.1016/j.neo.2014.08.010
卷: 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
所属项目编号: 81030012 ; 81330010 ; 81390354 ; 1-13-BS-225
项目资助者: National Institutes of Health (NIH) ; National Natural Science Foundation of China ; American Diabetes Association
WOS记录号: WOS:000345516900003
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/64833
Appears in Collections:北京大学第三临床医学院_超声诊断科_期刊论文

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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

Recommended Citation:
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.
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