S7 Mouse lung adenocarcinoma cell lines reveal PRL2C2 as a novel lung tumour promoter
| Autor: | M Spella, Nikolaos I. Kanellakis, Ian D. Pavord, Georgios T. Stathopoulos, Ioannis Psallidas, Dimitra E. Zazara, Malamati Vreka, Ioanna Giopanou, Antonia Marazioti, Theodora Agalioti, Anastassios D. Giannou, NM Rahman, Ioannis Lilis, Mario A.A. Pepe |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Pulmonary and Respiratory Medicine Genetically modified mouse Pathology medicine.medical_specialty education Cell Cancer Biology medicine.disease medicine.disease_cause 03 medical and health sciences 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure Cell culture 030220 oncology & carcinogenesis medicine Cancer research Gene silencing Adenocarcinoma KRAS Lung cancer |
| Popis: | Background Carcinogen-inflicted human cancers, including lung tumours harbour thousands of mutations per genome, most of which are unknown (Garraway, LA et al, Cell 2013;153:17–37). Aim To develop a faithful mouse model of human tobacco carcinogen-induced lung adenocarcinoma suitable for the identification of novel oncogenic genes and pathways. Methods We repeatedly managed to obtain several murine lung adenocarcinoma cell lines (MLA) by chronically exposing various mouse strains to different tobacco carcinogens. MLA were characterised for cancer stemness and oncogenes, as well as global gene expression. Results To date, 12 MLA cell lines have been derived from Wt and transgenic mice on the FVB, Balb/c, and C57BL/6 strains by means of urethane or diethylnitrosamine exposure. All MLA were immortal, phenotypically stable, and indefinitely passaged in vitro over a period of over 18 months and/or 60 passages. In addition, all cell lines were oncogenic, transplantable, metastatic, and uniformly lethal in vivo. Interestingly, MLA displayed Kras mutations in codon 61, mono- or bi-allelic Trp53 loss, and expression of lung cancer stemness factors Itgb3 and Lgr6, in amazing similarity to human lung cancers. Microarray revealed that all MLA cell lines heavily overexpressed Prl2c2, encoding proliferin, in comparison to the native lungs. Prl2c2 silencing diminished MLA proliferation and stemness, to a degree comparable with Itgb3 interference. Conclusions MLA are faithful models of human lung adenocarcinoma that led to the discovery of Prl2c2 as a candidate lung tumour promoter. Funding European Research Council Starting Independent Investigator Grant #260524. Respire 2 European Respiratory Society Fellowship, European Respiratory Society Short Term Research Fellowship. |
| Databáze: | OpenAIRE |
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