Animal model of Pancreatic Cancer

我们正在利用一种具有组织特异性表达突变kras和-P53基因的胰腺癌基因工程小鼠模型。LSL-Kras G12D、p53 R172 H和Pdx-1-Cre的杂交产生三突变体，通常称为KPC小鼠，其PDAC的中位生存期约为5个月，到12个月时死亡率几乎为100%。KPC小鼠忠实地再现了人类PDAC的发展和进展。为了确定MIF和NO在PDAC中的作用，我们进一步设计了该模型来生成iNOS-和MIF-缺陷的KPC模型。本课题的研究进展主要包括：1)iNOS-和mif -缺失小鼠胰腺癌模型的建立；2)iNOS-缺失可提高胰腺癌小鼠的存活率。在这项正在进行的研究中，我们目前正在研究no介导的肿瘤进展的机制。此外，基于我们对MIF与人类PDAC中疾病侵袭性的关联及其在疾病进展和转移中的机制作用的研究，我们正在使用MIF缺失的胰腺癌小鼠模型来确定其在肿瘤发生和进展中的作用，并评估其作为候选治疗靶点的潜力。

We are utilizing a genetically engineered mouse model of pancreatic cancer with tissue specific expression of mutant-KRAS and -P53 gene. Crossbreeding of LSL-Kras G12D, p53 R172 H and Pdx-1-Cre generates the triple mutants, commonly known as KPC mice, which develop PDAC with a median survival of approximately 5 months and almost 100% mortality by 12 months. The KPC mice faithfully recapitulate the development and progression of human PDAC. To determine the role of MIF and NO in PDAC, we have further engineered this model to generate both the iNOS- and MIF-deficient KPC models. The summary of our progress in this project includes:1) Generation of iNOS- and MIF-deficient mouse model of pancreatic cancer2) iNOS-deficiency enhances the survival in mice with pancreatic cancer.In this ongoing study, we are currently investigating the mechanism of NO-mediated tumor progression. Furthermore, based on our investigation of MIF showing its association with disease aggressiveness in human PDAC and its mechanistic role in disease progression and metastasis, we are using MIF-deficient pancreatic cancer mouse model to determine its role in tumor development and progression and to assess its potential as a candidate therapeutic target.