Journal article
MYC Deregulation and PTEN Loss Model Tumor and Stromal Heterogeneity of Aggressive Triple-Negative Breast Cancer
Nature communications, v 14(1), pp 5665-5665
13 Sep 2023
PMID: 37704631
Featured in Collection : UN Sustainable Development Goals @ Drexel
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.
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Details
- Title
- MYC Deregulation and PTEN Loss Model Tumor and Stromal Heterogeneity of Aggressive Triple-Negative Breast Cancer
- Creators
- Zinab O. Doha - Oregon Health & Science UniversityXiaoyan Wang - Oregon Health & Science UniversityNicholas L. Calistri - Oregon Health & Science UniversityJennifer Eng - Oregon Health & Science UniversityColin J. Daniel - Oregon Health & Science UniversityLuke Ternes - Oregon Health & Science UniversityEun Na Kim - Oregon Hlth & Sci Univ, Dept Biomed Engn, Portland, OR USACarl Pelz - Oregon Health & Science UniversityMichael Munks - Oregon Health & Science UniversityCourtney Betts - Oregon Health & Science UniversitySunjong Kwon - Oregon Health & Science UniversityElmar Bucher - Oregon Health & Science UniversityXi Li - Oregon Health & Science UniversityTrent Waugh - Oregon Health & Science UniversityZuzana Tatarova - Oregon Health & Science UniversityDylan Blumberg - Oregon Health & Science UniversityAaron Ko - Oregon Health & Science UniversityNell Kirchberger - Oregon Health & Science UniversityJennifer A. Pietenpol - Vanderbilt University Medical CenterMelinda E. Sanders - Vanderbilt University Medical CenterEllen M. Langer - Oregon Health & Science UniversityMu-Shui Dai - Oregon Health & Science UniversityGordon Mills - Oregon Health & Science UniversityKoei Chin - Oregon Health & Science UniversityYoung Hwan Chang - Oregon Health & Science UniversityLisa M. Coussens - Oregon Health & Science UniversityJoe W. Gray - Oregon Health & Science UniversityLaura M. Heiser - Oregon Health & Science UniversityRosalie C. Sears - Oregon Health & Science University
- Publication Details
- Nature communications, v 14(1), pp 5665-5665
- Publisher
- NATURE PORTFOLIO
- Number of pages
- 21
- Grant note
- Prospect Creek Foundation P30 CA69533 / Knight Cancer Institute through NIH OHSU Knight Cancer Institute Brenden-Colson Center Foundation NCI T32CA254888; P50 CA098131 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA SAB210301 / Komen; Susan G. Komen Breast Cancer Foundation
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pediatrics
- Web of Science ID
- WOS:001087583700001
- Scopus ID
- 2-s2.0-85170841553
- Other Identifier
- 991021838596204721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Oncology