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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 (r=0.3, P<0.015, n=67) and in two distinct breast progression arrays, ChREBP protein also increased with malignant progression (P<0.001). 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 P<0.001), 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.

Original publication

DOI

10.1038/bjc.2013.765

Type

Journal article

Journal

Br J Cancer

Publication Date

04/02/2014

Volume

110

Pages

715 - 723

Keywords

Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Biomarkers, Tumor, Breast Neoplasms, Disease Progression, Female, Gene Expression Regulation, Neoplastic, Glucose Transporter Type 1, Humans, Hypoxia, Immunohistochemistry, MCF-7 Cells, Prognosis