详情页 - 四川省肿瘤医院知识库

当前位置：首页 > 详情页

Smad4 deficiency substitutes Cdkn2b but not Cdkn2a downregulation in pancreatic cancer following induction of genetic events in adult mice.

文献详情

资源类型：

Pubmed体系：

作者：

机构： [a]Laboratory of Gastroenterology & Hepatology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China [b]Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China [c]Laboratory of Animal Tumor Models/Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China [d]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, Chinese Academy of Sciences, Kunming, Yunnan, China [e]Key Laboratory of Tumor Immunological Prevention and Treatment of Yunnan Province, Central Laboratory of Yan’an Hospital, Affiliated to Kunming Medical University, Kunming, Yunnan, China [f]State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China [g]KIZ-SU Joint Laboratory of Animal Model and Drug Development, College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, China

出处：

DOI：

ISSN：

关键词： Pancreatic cancer Animal model Smad4 Rb1

摘要：

Minor progress in pancreatic cancer treatment and prognosis implies that more reliable animal models are urgently needed to decipher its molecular mechanisms and preclinical research. We recently reported a genetically engineered adult mouse model where Cdkn2b downregulation was required together with Cdkn2a downregulation to inactivate the Rb pathway. Besides, the role of Smad4, which is mutated more frequently than Cdkn2b in human pancreatic cancer, was determined critical on the development of the pancreas tumor by some reports. However, the impact of Smad4 deficiency in combination with PDAC-relevant mutations, such as Cdkn2a when induced in adult pancreas has not been completely elucidated in mice. Lentiviral delivered oncogene/tumor suppressors in adult pancreas. The development of pancreatic cancer was monitored. Hematoxylin and eosin staining and immunofluorescence were performed for pathological identification of the pancreatic cancer. Real-time polymerase chain reaction, immunofluorescence and western blot were used to test gene expression. Loss of Smad4 could cooperate with alterations of KRAS, Trp53, and Cdkn2a to induce pancreatic cancer in adult mice. The role of Smad4 was mainly in downregulating the expression of Cdkn2b and further inducing phosphorylation of the Rb1 protein. These findings show an essential role of Smad4 deficiency in pancreatic ductal adenocarcinoma (PDAC) formation. This model better recapitulates the adult onset, clonal origin, and genetic alterations in human PDAC and can be simply generated on a large-scale. Copyright © 2021. Published by Elsevier B.V.

基金：

语种：

PubmedID：

中科院(CAS)分区：

出版当年[2021]版：

大类 | 3 区医学

小类 | 4 区胃肠肝病学

最新[2023]版：

大类 | 2 区医学

小类 | 3 区胃肠肝病学

第一作者：

第一作者机构： [a]Laboratory of Gastroenterology & Hepatology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China [b]Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China [f]State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China

共同第一作者：

通讯作者：

通讯机构： [a]Laboratory of Gastroenterology & Hepatology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China [b]Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China [c]Laboratory of Animal Tumor Models/Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China [d]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, Chinese Academy of Sciences, Kunming, Yunnan, China [g]KIZ-SU Joint Laboratory of Animal Model and Drug Development, College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, China [*1]Laboratory of Animal Tumor Models, West China Hospital, Sichuan University, Chengdu, 610041, China. [*2]State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China.

推荐引用方式(GB/T 7714)：

APA：

MLA：

Smad4 deficiency substitutes Cdkn2b but not Cdkn2a downregulation in pancreatic cancer following induction of genetic events in adult mice.

文献详情

相关文献