AKT1(E17K) Is Oncogenic in Mouse Lung and Cooperates with Chemical Carcinogens in Inducing Lung Cancer

The hotspot AKT1(E17K) mutation in the pleckstrin homology domain of AKT1 occurs in approximately 0.6–2% of human lung cancers. Recently, we have demonstrated that AKT1(E17K) transforms immortalized human bronchial cells. Here by use of a transgenic Cre-inducible murine strain in the wild type Rosa2...

Descripción completa

Detalles Bibliográficos
Autores principales: Malanga, Donatella, Belmonte, Stefania, Colelli, Fabiana, Scarfò, Marzia, De Marco, Carmela, Oliveira, Duarte Mendes, Mirante, Teresa, Camastra, Caterina, Gagliardi, Monica, Rizzuto, Antonia, Mignogna, Chiara, Paciello, Orlando, Papparella, Serenella, Fagman, Henrik, Viglietto, Giuseppe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Research Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4747507/
https://www.ncbi.nlm.nih.gov/pubmed/26859676
http://dx.doi.org/10.1371/journal.pone.0147334
Descripción
Sumario:The hotspot AKT1(E17K) mutation in the pleckstrin homology domain of AKT1 occurs in approximately 0.6–2% of human lung cancers. Recently, we have demonstrated that AKT1(E17K) transforms immortalized human bronchial cells. Here by use of a transgenic Cre-inducible murine strain in the wild type Rosa26 (R26) locus (R26-AKT1(E17K) mice) we demonstrate that AKT1(E17K) is a bona-fide oncogene and plays a role in the development of lung cancer in vivo. In fact, we report that mutant AKT1(E17K) induces bronchial and/or bronchiolar hyperplastic lesions in murine lung epithelium, which progress to frank carcinoma at very low frequency, and accelerates tumor formation induced by chemical carcinogens. In conclusion, AKT1(E17K) induces hyperplasia of mouse lung epithelium in vivo and cooperates with urethane to induce the fully malignant phenotype.

Ejemplares similares