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Cancer Metab. 2018 Apr 3;6:5. doi: 10.1186/s40170-018-0175-6. eCollection 2018.

Metabolomics of oncogene-specific metabolic reprogramming during breast cancer.

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1Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556 USA.
2Harper Cancer Research Institute, University of Notre Dame, 1234 N Notre Dame Avenue, South Bend, IN 46617 USA.
3Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030 USA.
4Department of Applied and Computational Mathematics and Statistics, University of Notre Dame, Notre Dame, IN 46556 USA.



The complex yet interrelated connections between cancer metabolism and oncogenic driver genes are relatively unexplored but have the potential to identify novel biomarkers and drug targets with prognostic and therapeutic value. The goal of this study was to identify global metabolic profiles of breast tumors isolated from multiple transgenic mouse models and to identify unique metabolic signatures driven by these oncogenes.


Using mass spectrometry (GC-MS, LC-MS/MS, and capillary zone electrophoresis (CZE)-MS platforms), we quantified and compared the levels of 374 metabolites in breast tissue from normal and transgenic mouse breast cancer models overexpressing a panel of oncogenes (PyMT, PyMT-DB, Wnt1, Neu, and C3-TAg). We also compared the mouse metabolomics data to published human metabolomics data already linked to clinical data.


Through analysis of our metabolomics data, we identified metabolic differences between normal and tumor breast tissues as well as metabolic differences unique to each initiating oncogene. We also quantified the metabolic profiles of the mammary fat pad versus mammary epithelium by CZE-MS/MS. However, the differences between the tissues did not account for the majority of the metabolic differences between the normal mammary gland and breast tumor tissues. Therefore, the differences between the cohorts were unlikely due to cellular heterogeneity. Of the mouse models used in this study, C3-TAg was the only cohort with a tumor metabolic signature composed of ten metabolites that had significant prognostic value in breast cancer patients. Gene expression analysis identified candidate genes that may contribute to the metabolic reprogramming.


This study identifies oncogene-induced metabolic reprogramming within mouse breast tumors and compares the results to that of human breast tumors, providing a unique look at the relationship between and clinical value of oncogene initiation and metabolism during breast cancer.


Breast cancer; Metabolic reprogramming; Metabolomics; Oncogene; Transgenic mouse model

Conflict of interest statement

All animal experiments were approved and conducted in accordance with the University of Notre Dame Institution Animal Care and Use Committee guidelines (protocol # 15-10-2724).Not applicable.The authors declare that they have no competing interests.

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