@article{10902/9717,
year = {2014},
url = {http://hdl.handle.net/10902/9717},
abstract = {Genetically engineered mouse models (GEMMs) have dramatically improved our understanding of tumor evolution and therapeutic resistance. However, sequential genetic manipulation of gene expression and targeting of the host is almost impossible using conventional Cre-loxP-based models. We have developed an inducible dual-recombinase system by combining flippase-FRT (Flp-FRT) and Cre-loxP recombination technologies to improve GEMMs of pancreatic cancer. This enables investigation of multistep carcinogenesis, genetic manipulation of tumor subpopulations (such as cancer stem cells), selective targeting of the tumor microenvironment and genetic validation of therapeutic targets in autochthonous tumors on a genome-wide scale. As a proof of concept, we performed tumor cell-autonomous and nonautonomous targeting, recapitulated hallmarks of human multistep carcinogenesis, validated genetic therapy by 3-phosphoinositide-dependent protein kinase inactivation as well as cancer cell depletion and show that mast cells in the tumor microenvironment, which had been thought to be key oncogenic players, are dispensable for tumor formation},
publisher = {Nat Med. 2014 Nov;20(11):1340-7},
title = {A next-generation dual-recombinase system for time- and host-specific targeting of pancreatic cancer},
author = {Schönhuber, Nina and Seidler, Barbara and Schuck, Kathleen and Veltkamp, Christian and Schachtler, Christina and Zukowska, Magdalena and Eser, Stefan and Feyerabend, Thorsten B and Paul, Mariel C and Eser, Philipp and Klein, Sabine and Lowy, Andrew M and Banergee, Ruby and Yan, Fangtang and Lee, Chang-Lung and Moding, Everett J and Kirsch, David G and Scheideler, Angelika and Alessi, Dario R and Varela Egocheaga, Ignacio and Bradley, Allan and Kind, Alexander and Schnieke, Angelika E and Rodewald, Hans Reimer and Rad, Roland and Schmid, Roland M and Schneider, Günter and Saur, Dieter},
}