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Role of carbohydrate response element-binding protein (ChREBP) in generating an aerobic metabolic phenotype and in breast cancer progression

Airley, RE and McHugh, P and Evans, AR and Harris, B and Winchester, L and Buffa, FM and Al-Tameemi, W and Leek, R and Harris, AL (2014) Role of carbohydrate response element-binding protein (ChREBP) in generating an aerobic metabolic phenotype and in breast cancer progression. BRITISH JOURNAL OF CANCER, 110 (3). pp. 715-723. ISSN 0007-0920

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Abstract

Background: The lipogenic transcription factor carbohydrate response element-binding protein (ChREBP) may play a key role in malignant progression of breast cancer by allowing metabolic adaptations to take place in response to changes in oxygenation.

Methods: Immunohistochemical analysis of ChREBP was carried out in human breast tumour tissue microarrays representative of malignant progression from normal breast through to metastatic cancer. The ChREBP protein and mRNA expressions were then analysed in a series of breast cancers for correlative analysis with common and breast-specific hypoxia signatures, and survival.

Results: In invasive ductal carcinoma, ChREBP correlated significantly with mean ‘downregulated’ hypoxia scores (r¼0.3, Po0.015, n¼67) and in two distinct breast progression arrays, ChREBP protein also increased with malignant progression (Po0.001). However, bioinformatic analysis of a large data set (2136 cases) revealed an apparent reversal in the relationship between ChREBP mRNA level and clinical outcome – not only being significantly correlated with increased survival (log rank Po0.001), but also downregulated in malignant tissue compared with adjacent normal tissue.

Conclusion: The ChREBP expression may be reflective of an aerobic metabolic phenotype that may conflict with hypoxia-induced signalling but provide a mechanism for growth at the oxygenated edge of the tumours.

Item Type: Article
Additional Information: Copyright Cancer Research UK
Uncontrolled Keywords: 1112 Oncology And Carcinogenesis
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Divisions: Pharmacy & Biomolecular Sciences
Publisher: NATURE PUBLISHING GROUP
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Date Deposited: 13 Nov 2015 13:56
Last Modified: 13 Nov 2015 13:56
DOI or Identification number: 10.1038/bjc.2013.765
URI: http://researchonline.ljmu.ac.uk/id/eprint/1724

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