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Cancer & Metabolism
Published in: Cancer & Metabolism 1/2018

Open Access 01-12-2018 | Research

Metabolomics of oncogene-specific metabolic reprogramming during breast cancer

Authors: Chen Dai, Jennifer Arceo, James Arnold, Arun Sreekumar, Norman J. Dovichi, Jun Li, Laurie E. Littlepage

Published in: Cancer & Metabolism | Issue 1/2018

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Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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.
Appendix
Available only for authorised users
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Metadata
Title
Metabolomics of oncogene-specific metabolic reprogramming during breast cancer
Authors
Chen Dai
Jennifer Arceo
James Arnold
Arun Sreekumar
Norman J. Dovichi
Jun Li
Laurie E. Littlepage
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Cancer & Metabolism / Issue 1/2018
Electronic ISSN: 2049-3002
DOI
https://doi.org/10.1186/s40170-018-0175-6

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