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Kanellakis, N.I.* ; Giannou, A.D.* ; Pepe, M. ; Αgalioti, T.* ; Zazara, D.E.* ; Giopanou, I.* ; Psallidas, I.* ; Spella, M.* ; Μarazioti, A.* ; Arendt, K.A.M. ; Lamort, A.-S. ; Tsaniras, S.C.* ; Taraviras, S.* ; Papadaki, H.* ; Lilis, I.* ; Stathopoulos, G.T.

Tobacco chemical-induced mouse lung adenocarcinoma cell lines pin the prolactin orthologue proliferin as a lung tumour promoter.

Carcinogenesis 40, 1352-1362 (2019)
Publ. Version/Full Text Postprint Research data DOI PMC
Open Access Green
Lung adenocarcinoma (LADC) is the leading cause of cancer death worldwide. Nevertheless, syngeneic mouse models of the disease are sparse, and cell lines suitable for transplantable and immunocompetent mouse models of LADC remain unmet needs. We established multiple mouse LADC cell lines by repeatedly exposing two mouse strains (FVB, Balb/c) to the tobacco carcinogens urethane or diethylnitrosamine and by culturing out the resulting lung tumours for prolonged periods of time. Characterization of the resulting cell lines (n = 7) showed that they were immortal and phenotypically stable in vitro, and oncogenic, metastatic and lethal in vivo. The primary tumours that gave rise to the cell lines, as well as secondary tumours generated by transplantation of the cell lines, displayed typical LADC features, such as glandular architecture and mucin and thyroid transcription factor 1 expression. Moreover, these cells exhibited marked molecular similarity with human smokers' LADC, including carcinogen-specific Kras point mutations (Kras(Q61R) in urethane- and Kras(Q61H) in diethylnitrosamine-triggered cell lines) and Trp53 deletions and displayed stemness features. Interestingly, all cell lines overexpressed proliferin, a murine prolactin orthologue, which functioned as a lung tumour promoter. Furthermore, prolactin was overexpressed and portended poor prognosis in human LADC. In conclusion, we report the first LADC cell lines derived from mice exposed to tobacco carcinogens. These cells closely resemble human LADC and provide a valuable tool for the functional investigation of the pathobiology of the disease.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Kras ; Lung Adenocarcinoma ; Trp53 ; Carcinogen ; Tobacco Chemical; Mutational Signatures; Cancer; Models; Expression; Gene; Activation; Lessons; Family
ISSN (print) / ISBN 0143-3334
e-ISSN 1460-2180
Journal Carcinogenesis
Quellenangaben Volume: 40, Issue: 11, Pages: 1352-1362 Article Number: , Supplement: ,
Publisher Oxford University Press
Publishing Place Great Clarendon St, Oxford Ox2 6dp, England
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Lung Health and Immunity (LHI)