Activation of PI3K and deletion of p53 in keratin 15-expressing mouse mammary cells induces tumor heterogeneity and plasticity modeling metaplastic breast cancer.

ABSTRACT: Although relatively rare, metaplastic breast cancer responds poorly to traditional therapies compared to other subtypes. Accordingly, there is a need for novel animal models to understand its pathogenesis and plasticity. Since alterations in PIK3CA and TP53 genes are common in metaplastic breast cancer, we generated a mouse model of metaplastic breast cancer by driving Pik3ca activation and Trp53 loss in keratin 15-expressing mammary cells. In this model, male and female mice developed spontaneous mammary lesions, with malignancy reliant on loss of both Trp53 alleles. Importantly, tumors of this model are heterogeneous and resemble the mixed histology of metaplastic breast cancer by exhibiting squamous cell carcinoma, carcinosarcoma, and sarcoma features. We developed mammary cell lines fr

SUBMITTER: Nguyen KA 

PROVIDER: S-EPMC12438019 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature