Journal article
c-Myc and Her2 cooperate to drive a stem-like phenotype with poor prognosis in breast cancer
Oncogenesis, Vol.33(30), pp.3992-4002
2014
Abstract
The HER2 (ERBB2) and MYC genes are commonly amplified in breast cancer, yet little is known about their molecular and clinical interaction. Using a novel chimeric mammary transgenic approach and in vitro models, we demonstrate markedly increased self-renewal and tumour-propagating capability of cells transformed with Her2 and c-Myc. Coexpression of both oncoproteins in cultured cells led to the activation of a c-Myc transcriptional signature and acquisition of a self-renewing phenotype independent of an epithelial–mesenchymal transition programme or regulation of conventional cancer stem cell markers. Instead, Her2 and c-Myc cooperated to induce the expression of lipoprotein lipase, which was required for proliferation and self-renewal in vitro. HER2 and MYC were frequently coamplified in breast cancer, associated with aggressive clinical behaviour and poor outcome. Lastly, we show that in HER2+ breast cancer patients receiving adjuvant chemotherapy (but not targeted anti-Her2 therapy), MYC amplification is associated with a poor outcome. These findings demonstrate the importance of molecular and cellular context in oncogenic transformation and acquisition of a malignant stem-like phenotype and have diagnostic and therapeutic consequences for the clinical management of HER2+ breast cancer.
Details
- Title
- c-Myc and Her2 cooperate to drive a stem-like phenotype with poor prognosis in breast cancer
- Authors/Creators
- R. Nair (Author/Creator) - Garvan Institute of Medical ResearchD.L. Roden (Author/Creator) - Garvan Institute of Medical ResearchW.S. Teo (Author/Creator) - Garvan Institute of Medical ResearchA. McFarland (Author/Creator) - Garvan Institute of Medical ResearchS. Junankar (Author/Creator) - Garvan Institute of Medical ResearchS. Ye (Author/Creator) - Garvan Institute of Medical ResearchA. Nguyen (Author/Creator) - Garvan Institute of Medical ResearchJ. Yang (Author/Creator) - Garvan Institute of Medical ResearchI. Nikolic (Author/Creator) - Garvan Institute of Medical ResearchM. Hui (Author/Creator) - Garvan Institute of Medical ResearchA. Morey (Author/Creator) - UNSW SydneyJ. Shah (Author/Creator) - UNSW SydneyA.D. Pfefferle (Author/Creator) - Lineberger Comprehensive Cancer Center, Chapel Hill, USAJ. Usary (Author/Creator) - Lineberger Comprehensive Cancer Center, Chapel Hill, USAC. Selinger (Author/Creator) - Royal Prince Alfred HospitalL.A Baker (Author/Creator) - Garvan Institute of Medical ResearchN. Armstrong (Author/Creator) - The University of SydneyM.J. Cowley (Author/Creator) - Garvan Institute of Medical ResearchM.J. Naylor (Author/Creator) - Garvan Institute of Medical ResearchC.J. Ormandy (Author/Creator) - Garvan Institute of Medical ResearchS.R. Lakhani (Author/Creator) - Royal Brisbane and Women's HospitalJ.I. Herschkowitz (Author/Creator) - Baylor College of MedicineC.M. Perou (Author/Creator) - Lineberger Comprehensive Cancer Center, Chapel Hill, USAW. Kaplan (Author/Creator) - Garvan Institute of Medical ResearchS.A. O'Toole (Author/Creator) - Garvan Institute of Medical ResearchA. Swarbrick (Author/Creator) - Garvan Institute of Medical Research
- Publication Details
- Oncogenesis, Vol.33(30), pp.3992-4002
- Publisher
- Nature Publishing Group
- Identifiers
- 991005541327707891
- Murdoch Affiliation
- Murdoch University
- Language
- English
- Resource Type
- Journal article
UN Sustainable Development Goals (SDGs)
This output has contributed to the advancement of the following goals:
Source: InCites
Metrics
51 Record Views
InCites Highlights
These are selected metrics from InCites Benchmarking & Analytics tool, related to this output
- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.108 Molecular & Cell Biology - Cancer & Development
- 1.108.591 Cancer Stem Cells
- Web Of Science research areas
- Biochemistry & Molecular Biology
- Cell Biology
- Genetics & Heredity
- Oncology
- ESI research areas
- Molecular Biology & Genetics