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 KrasG12D/+/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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Carcinogenesis / genetics
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Carcinogenesis / metabolism
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Carcinogenesis / pathology
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Cell Differentiation
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Cell Transformation, Neoplastic / genetics
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Cell Transformation, Neoplastic / metabolism
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Cell Transformation, Neoplastic / pathology
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DNA Damage / genetics*
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Epithelial-Mesenchymal Transition / genetics
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Female
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Humans
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Lung Neoplasms / genetics*
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Lung Neoplasms / metabolism
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Lung Neoplasms / pathology
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Male
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Mice
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Mice, Knockout
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Neuroendocrine Tumors / genetics*
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Neuroendocrine Tumors / metabolism
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Neuroendocrine Tumors / pathology
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Prognosis
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Proto-Oncogene Proteins / deficiency*
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Proto-Oncogene Proteins / genetics*
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Proto-Oncogene Proteins p21(ras) / genetics
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Signal Transduction
Substances
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MEN1 protein, human
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Men1 protein, mouse
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Proto-Oncogene Proteins
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Hras protein, mouse
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Proto-Oncogene Proteins p21(ras)