用于KRAS转化的人胰腺导管上皮细胞模型。

Human pancreatic duct epithelial cell model for KRAS transformation.

作者信息

Radulovich Nikolina, Qian Jia-ying, Tsao Ming-Sound

机构信息

Division of Applied Molecular Oncology, Ontario Cancer Institute, University Health Network, Ontario, Canada.

出版信息

Methods Enzymol. 2008;439:1-13. doi: 10.1016/S0076-6879(07)00401-6.

DOI:10.1016/S0076-6879(07)00401-6

PMID:18374152

Abstract

Mutations on the KRAS gene occur early during pancreatic duct cell carcinogenesis and have been identified in up to 90% of ductal adenocarcinoma. However, the functional role of KRAS mutations in the malignant transformation of normal pancreatic duct epithelial cells into cancer cells remains unknown. We have developed an in vitro model for KRAS transformation using near-normal HPV-16E6E7-immortalized human pancreatic ductal epithelial (HPDE-E6E7) cells. The expression of mutant KRAS(G12V) in HPDE cells by retroviral transduction resulted in weak tumorigenic transformation, with tumors formed in 50% of immune-deficient scid mice implanted by these KRAS-transformed cells. The model provides an opportunity to dissect further the molecular and cellular mechanisms associated with human pancreatic duct cell carcinogenesis.

摘要

KRAS基因的突变发生在胰腺导管细胞癌变的早期，在高达90%的导管腺癌中已被发现。然而，KRAS突变在正常胰腺导管上皮细胞向癌细胞恶性转化中的功能作用仍不清楚。我们利用接近正常的HPV-16E6E7永生化人胰腺导管上皮（HPDE-E6E7）细胞建立了一种KRAS转化的体外模型。通过逆转录病毒转导在HPDE细胞中表达突变型KRAS（G12V）导致弱致瘤转化，这些KRAS转化细胞植入的免疫缺陷scid小鼠中有50%形成了肿瘤。该模型为进一步剖析与人类胰腺导管细胞癌变相关的分子和细胞机制提供了机会。