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

CORC > 昆明动物研究所 > 昆明动物研究所 > 动物模型与人类重大疾病机理重点实验室

	CDKN2B deletion is essential for pancreatic cancer development instead of unmeaningful co-deletion due to juxtaposition to CDKN2A
	Shi P*4; Jiao B 4; Chen C 2; Zhou X 2,3; Lai R 2; Tu Q 2,3; Hao J 4; Sun B 2,3; Yang D 2,3; An S 2,3
刊名	Oncogene
	2017
卷号	期号:页码:publication online
英文摘要	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.
语种	英语
资助机构	This work was supported by by the ‘Strategic Priority Research Program’ of the Chinese Academy of Sciences (grant no. XDB13020400 to PS and XDA 01040403 to XZ), the National Natural Science Foundation of China (NSFC, 81472862) and the Top Talents Program of Yunnan Province, China (2012HA014) to XZ. ; This work was supported by by the ‘Strategic Priority Research Program’ of the Chinese Academy of Sciences (grant no. XDB13020400 to PS and XDA 01040403 to XZ), the National Natural Science Foundation of China (NSFC, 81472862) and the Top Talents Program of Yunnan Province, China (2012HA014) to XZ. ; This work was supported by by the ‘Strategic Priority Research Program’ of the Chinese Academy of Sciences (grant no. XDB13020400 to PS and XDA 01040403 to XZ), the National Natural Science Foundation of China (NSFC, 81472862) and the Top Talents Program of Yunnan Province, China (2012HA014) to XZ. ; This work was supported by by the ‘Strategic Priority Research Program’ of the Chinese Academy of Sciences (grant no. XDB13020400 to PS and XDA 01040403 to XZ), the National Natural Science Foundation of China (NSFC, 81472862) and the Top Talents Program of Yunnan Province, China (2012HA014) to XZ.
内容类型	期刊论文
源URL	[http://159.226.149.26:8080/handle/152453/12040]
专题	昆明动物研究所_动物模型与人类重大疾病机理重点实验室昆明动物研究所_遗传资源与进化国家重点实验室昆明动物研究所_动物毒素室昆明动物研究所_进化与功能基因组学昆明动物研究所_肿瘤生物学昆明动物研究所_肿瘤干细胞生物学昆明动物研究所_发育的印迹调控与进化学昆明动物研究所_中国科学院昆明灵长类研究中心
通讯作者	ship@mail.kiz.ac.cn; zhaoxudong@mail.kiz.ac.cn
作者单位	1.Kunming Primate Research Center, Chinese Academy of Sciences, Kunming, China 2.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; 3.Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, China 4.State Key Laboratory of Genetic Resources and Evolution, Laboratory of Evolutionary and Functional Genomics, Kunming Institute of Zoology, 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	Shi P,Jiao B,Chen C,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	Shi P.,Jiao B.,Chen C.,Zhou X.,Lai R.,...&Zhao X.(2017).CDKN2B deletion is essential for pancreatic cancer development instead of unmeaningful co-deletion due to juxtaposition to CDKN2A.Oncogene,(),publication online.
MLA	Shi P,et al."CDKN2B deletion is essential for pancreatic cancer development instead of unmeaningful co-deletion due to juxtaposition to CDKN2A".Oncogene .*(2017):publication online.