Ottenhof Niki A, Milne Anya N A, Morsink Folkert H M, Drillenburg Paul, Ten Kate Fiebo J W, Maitra Anirban, Offerhaus G Johan
Department of Pathology, University Medical Center, Utrecht, the Netherlands.
Arch Pathol Lab Med. 2009 Mar;133(3):375-81. doi: 10.5858/133.3.375.
Pancreatic cancer has a poor prognosis with a 5-year survival of less than 5%. Early detection is at present the only way to improve this outlook. This review focuses on the recent advances in our understanding of pancreatic carcinogenesis, the scientific evidence for a multistaged tumor progression, and the role genetically engineered mouse models can play in recapitulating the natural course and biology of human disease.
To illustrate the stepwise tumor progression of pancreatic cancer and genetic alterations within the different stages of progression and to review the findings made with genetically engineered mouse models concerning pancreatic carcinogenesis.
A review of recent literature on pancreatic tumorigenesis and genetically engineered mouse models.
Pancreatic cancer develops through stepwise tumor progression in which preinvasive stages, called pancreatic intraepithelial neoplasia, precede invasive pancreatic cancer. Genetic alterations in oncogenes and tumor suppressor genes underlying pancreatic cancer are also found in pancreatic intraepithelial neoplasia. These mutations accumulate during progression through the consecutive stages of pancreatic intraepithelial neoplasia lesions. Also in genetically engineered mouse models of pancreatic ductal adenocarcinoma, tumorigenesis occurs through stepwise progression via consecutive mouse pancreatic intraepithelial neoplasia, and these models provide important tools for clinical applications. Nevertheless differences between mice and men still remain.
胰腺癌预后较差，5年生存率低于5%。目前，早期检测是改善这种预后的唯一方法。本综述重点关注我们对胰腺癌发生机制的最新认识进展、肿瘤多阶段进展的科学证据，以及基因工程小鼠模型在重现人类疾病自然病程和生物学特性方面所起的作用。
阐述胰腺癌的肿瘤逐步进展过程以及进展不同阶段的基因改变，并综述基因工程小鼠模型在胰腺癌发生机制方面的研究发现。
对近期有关胰腺肿瘤发生和基因工程小鼠模型的文献进行综述。
胰腺癌通过肿瘤逐步进展而发生，在侵袭性胰腺癌之前存在称为胰腺上皮内瘤变的非侵袭性阶段。胰腺癌相关的癌基因和肿瘤抑制基因的基因改变在胰腺上皮内瘤变中也有发现。这些突变在胰腺上皮内瘤变病变的连续阶段进展过程中积累。同样，在胰腺导管腺癌的基因工程小鼠模型中，肿瘤发生也是通过连续的小鼠胰腺上皮内瘤变逐步进展的，这些模型为临床应用提供了重要工具。然而，小鼠和人类之间仍然存在差异。
