MYC regulation of Glutamine-Proline regulatory axis is key in Luminal B breast cancer

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Craze, Madeleine L., Cheung, Hayley, Jewa, Natasha, Coimbra, Nuno D.M., Soria, Daniele, El-Ansari, Rokaya, Aleskandarany, Mohammed A., Cheng, Kiu Wai, Diez-Rodriguez, Maria, Nolan, Christopher C., Ellis, Ian O., Rakha, Emad and Green, Andrew R. (2017) MYC regulation of Glutamine-Proline regulatory axis is key in Luminal B breast cancer. British Journal of Cancer . ISSN 1532-1827

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Abstract

Background: Altered cellular metabolism is a hallmark of cancer and some are reliant on Glutamine for sustained proliferation and survival. We hypothesise that the Glutamine-Proline regulatory axis has a key role in Breast cancer (BC) in the highly proliferative classes.

Methods: Glutaminase (GLS), pyrroline-5-carboxylate synthetase (ALDH18A1) and pyrroline-5-carboxylate reductase 1 (PYCR1) were assessed at DNA/mRNA/protein levels in large well-characterised cohorts.

Results: Gain of PYCR1 copy number and high PYCR1 mRNA was associated with luminal B tumours. High ALDH18A1 and high GLS protein expression was observed in the ER+/HER2- high proliferation class (Luminal B) compared with ER+/HER2- low proliferation class (Luminal A) (p=0.030 and p=0.022 respectively), however this was not observed with mRNA. Cluster analysis of the Glutamine-Proline regulatory axis genes revealed significant associations with molecular subtypes of breast cancer and patient outcome independent of standard clinicopathological parameters (p=0.012). High protein expression of the Glutamine-Proline enzymes were all associated with high MYC protein in Luminal B tumours only (p<0.001).

Conclusion: We provide comprehensive clinical data indicating that the Glutamine-Proline regulatory axis plays an important role in the aggressive subclass of luminal BC and is therefore a potential therapeutic target.

Item Type: Article
Keywords: metabolism, breast cancer, prognosis, Luminal B, glutamine, proline
Schools/Departments: University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Medicine > Division of Cancer and Stem Cells
Identification Number: https://doi.org/10.1038/bjc.2017.387
Depositing User: Eprints, Support
Date Deposited: 24 Oct 2017 11:11
Last Modified: 12 Jun 2018 09:05
URI: https://eprints.nottingham.ac.uk/id/eprint/47502

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