TY  - JOUR
AU  - Gewalt, Tabea
AU  - Dmitrieva, Anna M
AU  - Elsner, Felix
AU  - Zhao, Xinlei
AU  - Sieber, Daniel Dimitri
AU  - Kocak, Ilayda Gülsen
AU  - Yang, Qian
AU  - Orschel, Claudia Viktoria
AU  - Eckert, Naja Maria
AU  - Goebel, Bianca
AU  - Nill, Marieke
AU  - Peter, Franziska
AU  - Hartmann, Arndt
AU  - Beleggia, Filippo
AU  - Odenthal, Margarete
AU  - Reinhardt, Hans Christian
AU  - Ullrich, Roland Tillmann
AU  - Graw, Frederik
AU  - Meder, Lydia
TI  - TAT-CRE inhalation enables tumor induction corresponding to adenoviral Cre-recombinase in a lung cancer mouse model.
JO  - Communications biology
VL  - 8
IS  - 1
SN  - 2399-3642
CY  - London
PB  - Springer Nature
M1  - DKFZ-2025-00999
SP  - 741
PY  - 2025
AB  - Cre-recombinase inducible model systems are extensively used in cancer research to manipulate gene expression in specific tissues and induce autochthonous tumor growth. These systems often involve the cross-breeding of genetically engineered organisms containing loxP-flanked alleles with those expressing Cre-recombinase. This approach, while effective, has the challenge of requiring high numbers of animals due to breeding requirements. Other frequently used tumor induction methods in cancer research involve the direct application of viral Cre-recombinase vectors. This approach presents the challenge of the accessibility of facilities that meet the necessary safety level. In this context, we perform a comprehensive comparison between TAT-CRE (biosafety level S1) and adenoviral Cre-recombinase induced (biosafety level S2) lung adenocarcinomas driven by KrasG12D expression and Trp53 depletion. We use in vivo lung tumor monitoring via computed tomography, single-cell RNA sequencing, immunohistochemistry and flow cytometry to elucidate similarities and differences between TAT-CRE and adenoviral Cre-recombinase induced lung adenocarcinomas. TAT-CRE induced lung tumors present differences in micro-vessels and macrophages but with corresponding tumor onset and growth characteristics compared to adenoviral-Cre recombinase induced lung tumors. Taken together, TAT-CRE is a valuable genetic engineering safety level S1 alternative for cancer induction and may be implemented in other cancer models than lung cancer.
KW  - Animals
KW  - Integrases: genetics
KW  - Integrases: metabolism
KW  - Integrases: administration & dosage
KW  - Lung Neoplasms: genetics
KW  - Lung Neoplasms: pathology
KW  - Lung Neoplasms: metabolism
KW  - Mice
KW  - Adenoviridae: genetics
KW  - Disease Models, Animal
KW  - Adenocarcinoma of Lung: genetics
KW  - Adenocarcinoma of Lung: pathology
KW  - Administration, Inhalation
KW  - Mice, Inbred C57BL
KW  - Tumor Suppressor Protein p53: genetics
KW  - Cre recombinase (NLM Chemicals)
KW  - Integrases (NLM Chemicals)
KW  - Tumor Suppressor Protein p53 (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:40360735
DO  - DOI:10.1038/s42003-025-08146-0
UR  - https://inrepo02.dkfz.de/record/301327
ER  -