MYC Deregulation and PTEN Loss Model Tumor and Stromal Heterogeneity of Aggressive Triple-Negative Breast Cancer
-
Published:2023-09-13
Issue:1
Volume:14
Page:
-
ISSN:2041-1723
-
Container-title:Nature Communications
-
language:en
-
Short-container-title:Nat Commun
Author:
Doha Zinab O., Wang Xiaoyan, Calistri Nicholas L.ORCID, Eng JenniferORCID, Daniel Colin J., Ternes Luke, Kim Eun Na, Pelz Carl, Munks Michael, Betts Courtney, Kwon Sunjong, Bucher Elmar, Li Xi, Waugh Trent, Tatarova Zuzana, Blumberg Dylan, Ko Aaron, Kirchberger Nell, Pietenpol Jennifer A., Sanders Melinda E., Langer Ellen M.ORCID, Dai Mu-ShuiORCID, Mills GordonORCID, Chin KoeiORCID, Chang Young HwanORCID, Coussens Lisa M.ORCID, Gray Joe W.ORCID, Heiser Laura M.ORCID, Sears Rosalie C.ORCID
Abstract
AbstractTriple-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.
Funder
U.S. Department of Health & Human Services | NIH | National Cancer Institute United States Department of Defense | United States Army | Army Medical Command | Congressionally Directed Medical Research Programs
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
Reference102 articles.
1. Fallahpour, S. et al. Breast cancer survival by molecular subtype: a population-based analysis of cancer registry data. CMAJ Open 5, E734–E739 (2017). 2. Dent, R. et al. Triple-negative breast cancer: clinical features and patterns of recurrence. Clin. Cancer Res. 13, 4429 (2007). 3. Tan, A. R. & Swain, S. M. Therapeutic strategies for triple-negative breast cancer. Cancer J. 14, 343–351 (2008). 4. Kaplan, H. G., Malmgren, J. A. & Atwood, M. T1N0 triple negative breast cancer: risk of recurrence and adjuvant chemotherapy. Breast J. 15, 454–460 (2009). 5. Won, K. A. & Spruck, C. Triple‑negative breast cancer therapy: current and future perspectives (Review). Int. J. Oncol. 57, 1245–1261 (2020).
Cited by
2 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
|
|