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MYC Deregulation and PTEN Loss Model Tumor and Stromal Heterogeneity of Aggressive Triple-Negative Breast Cancer
- Source :
- Nature Communications, Vol 14, Iss 1, Pp 1-21 (2023)
- Publication Year :
- 2023
- Publisher :
- Nature Portfolio, 2023.
-
Abstract
- 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: 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 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.
- Subjects :
- Science
Subjects
Details
- Language :
- English
- ISSN :
- 20411723
- Volume :
- 14
- Issue :
- 1
- Database :
- Directory of Open Access Journals
- Journal :
- Nature Communications
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.2f5efa1be7d149bcb492c236e0e02ed5
- Document Type :
- article
- Full Text :
- https://doi.org/10.1038/s41467-023-40841-6