title: A bioluminescent mouse model of proliferation to highlight early stages of pancreatic cancer: A suitable tool for preclinical studies.
abstract: Transgenic mouse models designed to recapitulate genetic and pathologic aspects of cancer are useful to study early stages of disease as well as its progression. Among several, two of the most sophisticated models for pancreatic ductal adenocarcinoma (PDAC) are the LSL-Kras(G12D/+);Pdx-1-Cre (KC) and LSL-Kras(G12D/+);LSL-Trp53(R172H/+);Pdx-1-Cre (KPC) mice, in which the Cre-recombinase regulated by a pancreas-specific promoter activates the expression of oncogenic Kras alone or in combination with a mutant p53, respectively. Non-invasive in vivo imaging offers a novel approach to preclinical studies introducing the possibility to investigate biological events in the spatio/temporal dimension. We recently developed a mouse model, MITO-Luc, engineered to express the luciferase reporter gene in cells undergoing active proliferation. In this model, proliferation events can be visualized non-invasively by bioluminescence imaging (BLI) in every body district in vivo. Here, we describe the development and characterization of MITO-Luc-KC- and -KPC mice. In these mice we have now the opportunity to follow PDAC evolution in the living animal in a time frame process. Moreover, by relating in vivo and ex vivo BLI and histopathological data we provide evidence that these mice could represents a suitable tool for pancreatic cancer preclinical studies. Our data also suggest that aberrant proliferation events take place early in pancreatic carcinogenesis, before tumour appearance.
authors.affiliation: Department of Research, Advanced Diagnostics and Technological Innovation, Regina Elena National Cancer Institute, Via Elio Chianesi 53, Rome 00144, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: de Latouliere
authors.affiliation: Department of Research, Advanced Diagnostics and Technological Innovation, Regina Elena National Cancer Institute, Via Elio Chianesi 53, Rome 00144, Italy. Electronic address: manni@ifo.it.
authors.forename: Isabella
authors.initials: I
authors.lastname: Manni
authors.affiliation: Department of Clinical and Molecular Medicine, Sapienza University of Rome, Via di Grottarossa 1035-1039, Rome 00189, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Iacobini
authors.affiliation: Department of Clinical and Molecular Medicine, Sapienza University of Rome, Via di Grottarossa 1035-1039, Rome 00189, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pugliese
authors.affiliation: Department of Experimental Oncology, Regina Elena National Cancer Institute, Via Elio Chianesi 53, Rome 00144, Italy.
authors.forename: Gian Luca
authors.initials: GL
authors.lastname: Grazi
authors.affiliation: Department of Experimental Oncology, Regina Elena National Cancer Institute, Via Elio Chianesi 53, Rome 00144, Italy.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Perri
authors.affiliation: Department of Molecular Biotechnologies and Health Sciences, University of Turin, Via Nizza 52, Torino 10126, Italy; Center for Experimental Research and Medical Studies, Città della Salute e della Scienza di Torino, Via Santena 5, Torino 10126, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Cappello
authors.affiliation: Department of Molecular Biotechnologies and Health Sciences, University of Turin, Via Nizza 52, Torino 10126, Italy; Center for Experimental Research and Medical Studies, Città della Salute e della Scienza di Torino, Via Santena 5, Torino 10126, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Novelli
authors.affiliation: Department of Clinical and Molecular Medicine, Sapienza University of Rome, Via di Grottarossa 1035-1039, Rome 00189, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Menini
authors.affiliation: Department of Research, Advanced Diagnostics and Technological Innovation, Regina Elena National Cancer Institute, Via Elio Chianesi 53, Rome 00144, Italy. Electronic address: piaggio@ifo.it.
authors.forename: Giulia
authors.initials: G
authors.lastname: Piaggio
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000235:genetics; D004195:Disease Models, Animal; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000235:genetics*; D008163:Luminescent Measurements / Q000379:methods; D008164:Luminescent Proteins / Q000235:genetics; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic / Q000235:genetics*; D008856:Microscopy, Fluorescence / Q000379:methods*; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000473:pathology*; D011230:Precancerous Conditions / Q000235:genetics / Q000473:pathology*
chemical_list: D008164:Luminescent Proteins; D008156:Luciferases
keywords: Comparative pathology; Disease animal models; Molecular imaging; Pancreatic cancer; Proliferation