Glutamate dehydrogenase (GLUD1) expression in breast cancer

Craze, Madeleine L.; El-Ansari, Rokaya; Aleskandarany, Mohammed A.; Cheng, Kiu Wai; Al-Farsi, Lutfi; Masisi, Brendah; Diez-Rodriguez, Maria; Nolan, Christopher C; Ellis, Ian O; Rakha, Emad A; Green, Andrew R

Abstract

Dysregulated cellular metabolism is regarded as one of the hallmarks of cancer with some tumours utilising the glutamine metabolism pathway for their sustained proliferation and survival. Glutamate dehydrogenase (GLUD1) is a key enzyme in glutaminolysis converting glutamate to α-Ketoglutarate for entry into the TCA cycle.
Breast cancer (BC) comprises a heterogeneous group of tumours in terms of molecular biology and clinical behaviour, and we have previously shown that altered glutamine metabolism varies substantially among the different molecular subtypes.
We hypothesise that the prognostic value of GLUD1 expression will differ between the BC molecular subtypes and may act as a potential therapeutic target for BC tumours.
Methods: GLUD1 was assessed at the DNA, mRNA (n=1,980) and protein (n=1,300) levels in large and well-characterised cohorts and correlated with clinicopathological parameters, molecular subtypes, patient outcome and treatments.
Results: There was a correlation between GLUD1 mRNA and GLUD1 protein expression which were highly expressed in low grade Luminal/ER+ BC (p

Citation

Craze, M. L., El-Ansari, R., Aleskandarany, M. A., Cheng, K. W., Al-Farsi, L., Masisi, B., Diez-Rodriguez, M., Nolan, C. C., Ellis, I. O., Rakha, E. A., & Green, A. R. (2019). Glutamate dehydrogenase (GLUD1) expression in breast cancer. Breast Cancer Research and Treatment, 174(1), 79–91. https://doi.org/10.1007/s10549-018-5060-z

• Journal Article Type: Article
• Acceptance Date: Nov 16, 2018
• Online Publication Date: Nov 23, 2018
• Publication Date: 2019-02
• Deposit Date: Nov 19, 2018
• Publicly Available Date: Nov 24, 2019
• Journal: Breast Cancer Research and Treatment
• Print ISSN: 0167-6806
• Electronic ISSN: 1573-7217
• Publisher: Springer Verlag
• Peer Reviewed: Peer Reviewed
• Volume: 174
• Issue: 1
• Pages: 79–91
• DOI: https://doi.org/10.1007/s10549-018-5060-z
• Keywords: GLUD1; breast cancer; prognosis; triple negative; glutamine; metabolism
• Public URL: https://nottingham-repository.worktribe.com/output/1281768
• Publisher URL: https://link.springer.com/article/10.1007%2Fs10549-018-5060-z
• Additional Information: Received: 9 November 2018; Accepted: 16 November 2018; First Online: 23 November 2018; : ; : The authors confirm that they do not have any conflict of interests to declare.; : This study was approved by the Nottingham Research Ethics Committee 2 under the title ‘Development of a molecular genetic classification of breast cancer’. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. All tissue samples from Nottingham used in this study were pseudo-anonymised and collected prior to 1st September 2006; therefore under the Human Tissue Act informed patient consent was not needed. Release of data was also pseudo-anonymised as per Human Tissue Act regulations. This article does not contain any studies with animals performed by any of the authors.
• Contract Date: Nov 19, 2018