MYC Deregulation and PTEN Loss Model Tumor and Stromal Heterogeneity of Aggressive Triple-Negative Breast Cancer
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Sep 13, 2023
- Source ID
- 10.1038/s41467-023-40841-6
Entities
People
- Aaron Ko
- Carl Pelz
- Colin J. Daniel
- Courtney Betts
- Dylan Blumberg
- Ellen M. Langer
- Elmar Bucher
- Eun Na Kim
- Gordon B. Mills
- Jennifer A. Pietenpol
- Jennifer Eng
- Joe W. Gray
- Koei Chin
- Laura M Heiser
- Lisa Coussens
- Luke Ternes
- Melinda E. Sanders
- Michael Munks
- Mu-Shui Dai
- Nell Kirchberger
- Nicholas L Calistri
- Rosalie C Sears
- Sunjong Kwon
- Trent Waugh
- Xi Li
- Xiaoyan Wang
- Young Hwan Chang
- Zinab O. Doha
- Zuzana Tatarova
Organizations
- Congressionally Directed Medical Research Programs
- National Cancer Institute