Conditional Expression of Oncogenic C-RAF in Mouse Pulmonary Epithelial Cells Reveals Differential Tumorigenesis and Induction of Autophagy Leading to Tumor Regression
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- Here we describe a novel conditional mouse lung tumor model for investigation of the pathogenesis of human lung cancer. On the basis of the frequent involvement of the Ras-RAF-MEK-ERK signaling pathway in human non-small cell lung carcinoma (NSCLC), we have explored the target cell availability, reversibility, and cell type specificity of transformation by oncogenic C-RAF. Targeting expression to alveolar type II cells or to Clara cells, the two likely precursors of human NSCLC, revealed differential tumorigenicity between these cells. WhereasHere we describe a novel conditional mouse lung tumor model for investigation of the pathogenesis of human lung cancer. On the basis of the frequent involvement of the Ras-RAF-MEK-ERK signaling pathway in human non-small cell lung carcinoma (NSCLC), we have explored the target cell availability, reversibility, and cell type specificity of transformation by oncogenic C-RAF. Targeting expression to alveolar type II cells or to Clara cells, the two likely precursors of human NSCLC, revealed differential tumorigenicity between these cells. Whereas expression of oncogenic C-RAF in alveolar type II cells readily induced multifocal macroscopic lung tumors independent of the developmental state, few tumors with type II pneumocytes features and incomplete penetrance were found when targeted to Clara cells. Induced tumors did not progress and were strictly dependent on the initiating oncogene. Deinduction of mice resulted in tumor regression due to autophagy rather than apoptosis. Induction of autophagic cell death in regressing lung tumors suggests the use of autophagy enhancers as a treatment choice for patients with NSCLC.…
Autor(en): | Fatih Ceteci, Jiajia Xu, Semra Ceteci, Emanuele Zanucco, Chitra Thakur, Ulf R. Rapp |
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URN: | urn:nbn:de:bvb:20-opus-134347 |
Dokumentart: | Artikel / Aufsatz in einer Zeitschrift |
Institute der Universität: | Medizinische Fakultät / Theodor-Boveri-Institut für Biowissenschaften |
Sprache der Veröffentlichung: | Englisch |
Titel des übergeordneten Werkes / der Zeitschrift (Englisch): | Neoplasia |
Erscheinungsjahr: | 2011 |
Band / Jahrgang: | 13 |
Heft / Ausgabe: | 11 |
Seitenangabe: | 1005-1018 |
Originalveröffentlichung / Quelle: | Neoplasia Volume 13, Issue 11, November 2011, Pages 1005-1018, IN1-IN17 |
DOI: | https://doi.org/10.1593/neo.11652 |
Allgemeine fachliche Zuordnung (DDC-Klassifikation): | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Freie Schlagwort(e): | Activation; Adenocarcinomas; Gene-expression; Human lung-cancer; In-vivo; Induced senescence; K-RAS; Kinase pathway; Model; P53 |
Datum der Freischaltung: | 19.03.2019 |
Lizenz (Deutsch): | CC BY-NC-ND: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell, Keine Bearbeitungen 4.0 International |