Mammary-specific expression of Trim24 establishes a mouse model of human metaplastic breast cancer.

ABSTRACT: Conditional overexpression of histone reader Tripartite motif containing protein 24 (TRIM24) in mouse mammary epithelia (Trim24^COE) drives spontaneous development of mammary carcinosarcoma tumors, lacking ER, PR and HER2. Human carcinosarcomas or metaplastic breast cancers (MpBC) are a rare, chemorefractory subclass of triple-negative breast cancers (TNBC). Comparison of Trim24^COE metaplastic carcinosarcoma morphology, TRIM24 protein levels and a derived Trim24^COE gene signature reveals strong correlation with human MpBC tumors and MpBC patient-derived xenograft (PDX) models. Global and single-cell tumor profiling reveal Met as a direct oncogenic target of TRIM24, leading to aberrant PI3K/mTOR activation. Here, we find that pharmacological inhibition of the

SUBMITTER: Shah VV 

PROVIDER: S-EPMC8433435 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature