MEN1 deficiency leads to neuroendocrine differentiation of lung cancer and disrupts the DNA damage response.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 32081882.
- Also identified by DOI 10.1038/s41467-020-14614-4 and PMC identifier 7035285.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
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<sup>G12D/+</sup>/Men1<sup>-/-</sup> 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.
Medical subject headings
- DNA Damage
- Lung Neoplasms
- Neuroendocrine Tumors
- Proto-Oncogene Proteins