This study investigates the oncogenic potential of the BRD4-NUT fusion protein in NUT carcinoma (NC). Using a genetically engineered mouse model (GEMM) expressing BRD4-NUT specifically in squamous epithelial cells, researchers demonstrate that the fusion protein alone is sufficient to drive malignant transformation.
Mice expressing BRD4-NUT developed aggressive tumors with 100% penetrance, confirming that the fusion protein alone is sufficient for malignant transformation. Treatment with BET bromodomain inhibitors (BETi) induced differentiation and tumor growth arrest, mirroring clinical responses observed in human NUT carcinoma.
BRD4-NUT inducible Knockin mouse model developed using: - Tamoxifen-inducible Cre recombinase (CreER(T2)) under the Sox2 promoter for temporal regulation of gene expression. - Internal Ribosome Entry Site (IRES) for bicistronic expression of BRD4-NUT and a reporter gene. - Reporter gene (e.g., luciferase or fluorescent protein) integrated for in vivo tracking of tumor development.
NUT carcinoma, BET inhibitors, BRD4-NUT fusion, Squamous cell carcinoma, Targeted therapy
Knockin mouse model, Flex technology, Tamoxifen-inducible CreER<sup>T2</sup>, IRES-mediated bicistronic expression, Reporter gene (fluorescence/luciferase)
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