A novel experimental model for human mixed acinar-ductal pancreatic cancer.

Abstract:

:Pancreatic cancer has remained refractory to treatment. In large part, this results from the lack of an animal model that mimics pancreatic cancer in man. We describe a novel experimental model of pancreatic cancer that shares the genetic background, histologic features and natural history of human mixed acinar-ductal carcinoma. Adult wild-type mice received an injection into the pancreatic duct of lentivirus coding two molecules, KrasG12D mutation and shRNA p53, which recapitulate the mechanisms of pancreatic cancer in humans. The lentivirus constructs also co-expressed the luciferase gene for in vivo imaging by bioluminescence using the Xenogen IVIS imaging system. Weeks post-injection wild-type mice develop pancreatic cancer with the same histologic characteristics and metastases observed with human pancreatic mixed acinar-ductal carcinoma. This novel approach represents the first pancreatic cancer model that does not involve alterations of embryonic development, which is inherent with transgenic mice or knockout mice models. This novel experimental human pancreatic cancer model can be used to more effectively test new anti-cancer drug to inhibit tumor progression in situ and to retard metastases. Furthermore, our method of injecting lentivirus containing oncogenes and molecules implicated in the development of pancreatic can be employed in diabetic and obese mice, two common metabolic conditions characterized by an increased incidence of pancreatic cancer.

journal_name

Carcinogenesis

journal_title

Carcinogenesis

authors

Doiron B,DeFronzo RA

doi

10.1093/carcin/bgx119

subject

Has Abstract

pub_date

2018-02-09 00:00:00

pages

180-190

issue

2

eissn

0143-3334

issn

1460-2180

pii

4585652

journal_volume

39

pub_type

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