title: AKT1E¹⁷K Is Oncogenic in Mouse Lung and Cooperates with Chemical Carcinogens in Inducing Lung Cancer.
abstract: The hotspot AKT1E17K mutation in the pleckstrin homology domain of AKT1 occurs in approximately 0.6-2% of human lung cancers. Recently, we have demonstrated that AKT1E17K transforms immortalized human bronchial cells. Here by use of a transgenic Cre-inducible murine strain in the wild type Rosa26 (R26) locus (R26-AKT1E17K mice) we demonstrate that AKT1E17K is a bona-fide oncogene and plays a role in the development of lung cancer in vivo. In fact, we report that mutant AKT1E17K 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, AKT1E17K induces hyperplasia of mouse lung epithelium in vivo and cooperates with urethane to induce the fully malignant phenotype.
authors: Dipartimento di Medicina Sperimentale e Clinica, Università Magna Graecia, Catanzaro, Italy.|BIOGEM-Istituto di Ricerche Genetiche, Ariano Irpino (AV), Italy.
authors: Donatella
authors: D
authors: Malanga
authors: BIOGEM-Istituto di Ricerche Genetiche, Ariano Irpino (AV), Italy.
authors: Stefania
authors: S
authors: Belmonte
authors: BIOGEM-Istituto di Ricerche Genetiche, Ariano Irpino (AV), Italy.
authors: Fabiana
authors: F
authors: Colelli
authors: BIOGEM-Istituto di Ricerche Genetiche, Ariano Irpino (AV), Italy.
authors: Marzia
authors: M
authors: Scarfò
authors: Dipartimento di Medicina Sperimentale e Clinica, Università Magna Graecia, Catanzaro, Italy.|BIOGEM-Istituto di Ricerche Genetiche, Ariano Irpino (AV), Italy.
authors: Carmela
authors: C
authors: De Marco
authors: Dipartimento di Medicina Sperimentale e Clinica, Università Magna Graecia, Catanzaro, Italy.
authors: Duarte Mendes
authors: DM
authors: Oliveira
authors: Dipartimento di Medicina Sperimentale e Clinica, Università Magna Graecia, Catanzaro, Italy.
authors: Teresa
authors: T
authors: Mirante
authors: Dipartimento di Scienze della Salute, Unità di Anatomia Patologica, Università Magna Graecia, Catanzaro, Italy.
authors: Caterina
authors: C
authors: Camastra
authors: IBFM-CNR, c/o Università Magna Graecia, Catanzaro, Italy.
authors: Monica
authors: M
authors: Gagliardi
authors: Dipartimento di Scienze Mediche e Chirurgiche, Università Magna Graecia, Catanzaro, Italy.
authors: Antonia
authors: A
authors: Rizzuto
authors: Dipartimento di Scienze della Salute, Unità di Anatomia Patologica, Università Magna Graecia, Catanzaro, Italy.
authors: Chiara
authors: C
authors: Mignogna
authors: Department of Veterinary Medicine and Animal Productions, Università Federico II, Napoli, Italy.
authors: Orlando
authors: O
authors: Paciello
authors: Department of Veterinary Medicine and Animal Productions, Università Federico II, Napoli, Italy.
authors: Serenella
authors: S
authors: Papparella
authors: Department of Clinical Pathology and Genetics, Sahlgrenska University Hospital, Göteborg, Sweden.
authors: Henrik
authors: H
authors: Fagman
authors: Dipartimento di Medicina Sperimentale e Clinica, Università Magna Graecia, Catanzaro, Italy.|BIOGEM-Istituto di Ricerche Genetiche, Ariano Irpino (AV), Italy.
authors: Giuseppe
authors: G
authors: Viglietto
mesh_terms: D000818:Animals; D001980:Bronchi / Q000187:drug effects / Q000473:pathology; D063646:Carcinogenesis / Q000187:drug effects / Q000235:genetics; D002273:Carcinogens / Q000494:pharmacology*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology; D005260:Female; D006801:Humans; D006965:Hyperplasia; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008175:Lung Neoplasms / Q000139:chemically induced* / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D009857:Oncogenes / Q000235:genetics*; D011247:Pregnancy; D017434:Protein Structure, Tertiary; D051057:Proto-Oncogene Proteins c-akt / Q000737:chemistry / Q000235:genetics*; D014520:Urethane / Q000494:pharmacology
chemical_list: D002273:Carcinogens; D014520:Urethane; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt