MYC Deregulation and PTEN Loss Model Tumor and Stromal Heterogeneity of Aggressive Triple-Negative Breast Cancer

MYC Deregulation and PTEN Loss Model Tumor and Stromal Heterogeneity of Aggressive Triple-Negative Breast Cancer

Blog Article

Abstract Triple-negative breast cancer (TNBC) patients have a poor prognosis and few treatment options.Mouse models of TNBC are important for development of new therapies, however, few mouse models represent the complexity of TNBC.Here, we develop a female TNBC murine model by mimicking two common TNBC mutations with high co-occurrence: Security Cables amplification of the oncogene MYC and deletion of the tumor suppressor PTEN.

This Myc;Ptenfl model develops heterogeneous triple-negative mammary tumors that display histological and molecular features commonly found in human TNBC.Our research involves deep molecular and spatial analyses on Myc;Ptenfl tumors including bulk and single-cell RNA-sequencing, and multiplex tissue-imaging.Through comparison with human TNBC, we demonstrate that this genetic mouse model develops mammary tumors with differential survival and therapeutic responses that closely resemble L-Citrulline the inter- and intra-tumoral and microenvironmental heterogeneity of human TNBC, providing a pre-clinical tool for assessing the spectrum of patient TNBC biology and drug response.