Experiments were performed in a genetically engineered mouse model of pancreatic cancer (KPC mice: LSL-Kras<sup>G12D/+</sup>; LSL-Trp53<sup>R172H/+</sup>; Pdx-1-Cre).
K-ras<sup>LSL-G12D/+</sup>:: p53<sup>LSL-R172H/+</sup>:: Pdx-1-Cre (KPC) mice are an established model of pancreatic cancer that specifically express mutants of both K-ras and p53 in the pancreas by using Pdx-1-Cre.
The LSL-Kras<sup>G12D/+</sup>; LSL-Trp53<sup>R172H/+</sup>; Pdx-1-Cre (KPC) mouse model represents an established and frequently used transgenic model to evaluate novel therapies in pancreatic cancer.
In all but two patients with pancreatic cancer, PDX-1 was expressed and was found positive in 7 patients with pancreatic cancer in which cytology was negative.
Down-regulation of PDX-1 expression inhibits pancreatic cancer cell growth in vitro and in vivo, implying its use as a potential therapeutic target for the treatment of pancreatic cancer.
To further explore the oncogenic activity of Aurora A kinase while attempting to develop a useful mouse model for pancreatic cancer, Aurora A kinase was targeted to pancreatic duodenal homeobox gene-1 (Pdx-1)-positive cells.
Furthermore, PDX-1 protein was found in all six freshly isolated human pancreas cancer specimens and two liver metastasis samples that were group-tested, suggesting the feasibility of using RIP-TK gene therapy in humans.