Nature communications, 2020-02, Vol.11 (1), p.1009-12, Article 1009
2020
Details
- Autor(en) / Beteiligte
- Titel
- MEN1 deficiency leads to neuroendocrine differentiation of lung cancer and disrupts the DNA damage response
- Ist Teil von
- Nature communications, 2020-02, Vol.11 (1), p.1009-12, Article 1009
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2020
- Link zum Volltext
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- The MEN1 gene, a tumor suppressor gene that encodes the protein menin, is mutated at high frequencies in neuroendocrine (NE) tumors; however, the biological importance of this gene in NE-type lung cancer in vivo remains unclear. Here, we established an ATII-specific Kras /Men1 driven genetically engineered mouse model and show that deficiency of menin results in the accumulation of DNA damage and antagonizes oncogenic Kras-induced senescence and the epithelial-to-mesenchymal transition during lung tumorigenesis. The loss of menin expression in certain human primary lung cancers correlates with elevated NE profiles and reduced overall survival.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2041-1723eISSN: 2041-1723DOI: 10.1038/s41467-020-14614-4Titel-ID: cdi_doaj_primary_oai_doaj_org_article_6fb64604831e428da09697a05d822f59
- Format
- –
- Schlagworte
- Alveoli, Animals, Carcinogenesis - genetics, Carcinogenesis - metabolism, Carcinogenesis - pathology, Cell Differentiation, Cell Transformation, Neoplastic - genetics, Cell Transformation, Neoplastic - metabolism, Cell Transformation, Neoplastic - pathology, Damage accumulation, Deoxyribonucleic acid, Differentiation, DNA, DNA damage, DNA Damage - genetics, Epithelial-Mesenchymal Transition - genetics, Female, Genetic engineering, Humans, Lung cancer, Lung Neoplasms - genetics, Lung Neoplasms - metabolism, Lung Neoplasms - pathology, Male, Mesenchyme, Mice, Mice, Knockout, Mutants, Neuroendocrine Tumors - genetics, Neuroendocrine Tumors - metabolism, Neuroendocrine Tumors - pathology, Prognosis, Proto-Oncogene Proteins - deficiency, Proto-Oncogene Proteins - genetics, Proto-Oncogene Proteins p21(ras) - genetics, Senescence, Signal Transduction, Tumor suppressor genes, Tumorigenesis, Tumors