CDKN2B deletion is essential for pancreatic cancer development instead of unmeaningful co-deletion due to juxtaposition to CDKN2A

	CDKN2B deletion is essential for pancreatic cancer development instead of unmeaningful co-deletion due to juxtaposition to CDKN2A
	Tu Q 1,2; Hao J 3; Sun B 1,2; Yang D 1,2; An S 1,2; Lv L 4; Jiao B 3; Chen C 1; Zhou X 1,2; Lai R 1; Shi P3 ; Zhao X1,4,5; Yan L 1,4; Dai H 1
	2017
发表期刊	Oncogene
卷号	期号:页码:publication online
摘要	Pancreatic cancer is among the deadliest malignancies; however, the genetic events that lead to pancreatic carcinogenesis in adults remain unclear. In vivo models in which these genetic alterations occur in adult animals may more accurately reflect the features of human cancer. In this study, we demonstrate that inactivation of Cdkn2b (p15ink4b) is necessary for induction of pancreatic cancer by oncogenic KRASG12D expression and inactivation of Tp53 and Cdkn2a in adult mouse pancreatic ductal cells (P60 or older). KRASG12D overexpression in these cells activated transforming growth factor-β signaling and expression of CDKN2B, which, along with CDKN2A, led to cellular senescence and protected cells from KRAS-mediated transformation via inhibition of retinoblastoma phosphorylation. These results show a critical role of CDKN2B inactivation in pancreatic carcinogenesis, and provide a useful adult animal model by genetic engineering via lentiviral delivery.
收录类别	SCI
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/12040
专题	科研部门_动物模型与人类重大疾病机理重点实验室遗传资源与进化国家重点实验室科研部门_天然药物功能蛋白质学科组（赖仞）科研部门_进化与功能基因组学（施鹏）科研部门_肿瘤干细胞生物学（赵旭东）科研部门_肿瘤生物学（陈策实）科研部门_发育的印迹调控与进化学（焦保卫）中国科学院昆明灵长类研究中心
作者单位	1.Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology, Kunming, China; 2.Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, China 3.State Key Laboratory of Genetic Resources and Evolution, Laboratory of Evolutionary and Functional Genomics, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China 4.Kunming Primate Research Center, Chinese Academy of Sciences, Kunming, China 5.KIZ-SU Joint Laboratory of Animal Model and Drug Development, College of Pharmaceutical Sciences, Soochow University, Suzhou, China
推荐引用方式 GB/T 7714	Tu Q,Hao J,Sun B,et al. CDKN2B deletion is essential for pancreatic cancer development instead of unmeaningful co-deletion due to juxtaposition to CDKN2A[J]. Oncogene,2017,():publication online.
APA	Tu Q.,Hao J.,Sun B.,Yang D.,An S.,...&Dai H.(2017).CDKN2B deletion is essential for pancreatic cancer development instead of unmeaningful co-deletion due to juxtaposition to CDKN2A.Oncogene,(),publication online.
MLA	Tu Q,et al."CDKN2B deletion is essential for pancreatic cancer development instead of unmeaningful co-deletion due to juxtaposition to CDKN2A".Oncogene .(2017):publication online.

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onc2017316a.pdf（5830KB）	期刊论文	出版稿	开放获取	CC BY-NC-SA	请求全文