Cancer research (Chicago, Ill.), 2013-10, Vol.73 (19), p.5974-5984
2013
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Details
- Autor(en) / Beteiligte
- Titel
- Notch1 Is Required for Kras-Induced Lung Adenocarcinoma and Controls Tumor Cell Survival via p53
- Ist Teil von
- Cancer research (Chicago, Ill.), 2013-10, Vol.73 (19), p.5974-5984
- Ort / Verlag
- Philadelphia, PA: American Association for Cancer Research
- Erscheinungsjahr
- 2013
- Quelle
- Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
- Beschreibungen/Notizen
- The Notch pathway has been implicated in a number of malignancies with different roles that are cell- and tissue-type dependent. Notch1 is a putative oncogene in non-small cell lung cancer (NSCLC) and activation of the pathway represents a negative prognostic factor. To establish the role of Notch1 in lung adenocarcinoma, we directly assessed its requirement in Kras-induced tumorigenesis in vivo using an autochthonous model of lung adenocarcinoma with concomitant expression of oncogenic Kras and deletion of Notch1. We found that Notch1 function is required for tumor initiation via suppression of p53-mediated apoptosis through the regulation of p53 stability. These findings implicate Notch1 as a critical effector in Kras-driven lung adenocarcinoma and as a regulator of p53 at a posttranslational level. Moreover, our study provides new insights to explain, at a molecular level, the correlation between Notch1 activity and poor prognosis in patients with NSCLC carrying wild-type p53. This information is critical for design and implementation of new therapeutic strategies in this cohort of patients representing 50% of NSCLC cases.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0008-5472eISSN: 1538-7445DOI: 10.1158/0008-5472.can-13-1384Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3791518
- Format
- –
- Schlagworte
- Adenocarcinoma - genetics, Adenocarcinoma - metabolism, Adenocarcinoma - pathology, Animals, Antineoplastic agents, Apoptosis, Biological and medical sciences, Blotting, Western, Carcinoma, Non-Small-Cell Lung - genetics, Carcinoma, Non-Small-Cell Lung - metabolism, Carcinoma, Non-Small-Cell Lung - pathology, Cell Cycle, Cell Proliferation, Cell Transformation, Neoplastic, Fluorescent Antibody Technique, Humans, Immunoenzyme Techniques, Lung Neoplasms - genetics, Lung Neoplasms - metabolism, Lung Neoplasms - pathology, Medical sciences, Mice, Mice, Knockout, Multiple tumors. Solid tumors. Tumors in childhood (general aspects), Mutation - genetics, Pharmacology. Drug treatments, Pneumology, Proto-Oncogene Proteins p21(ras) - physiology, Receptor, Notch1 - physiology, Signal Transduction, Tumor Cells, Cultured, Tumor Suppressor Protein p53 - chemistry, Tumor Suppressor Protein p53 - metabolism, Tumors, Tumors of the respiratory system and mediastinum