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

R. E. Airley, P. McHugh, A. R. Evans, B. Harris, L. Winchester, F. M. Buffa, W. Al-Tameemi, R. Leek, A. L. Harris

Research output: Contribution to journalArticle

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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 (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 languageEnglish
Pages (from-to)715-723
Number of pages9
JournalBritish Journal of Cancer
Volume110
Issue number3
DOIs
Publication statusPublished - 4 Feb 2014

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Response Elements
Carrier Proteins
Carbohydrates
Breast Neoplasms
Phenotype
Breast
Down-Regulation
Ductal Carcinoma
Messenger RNA
Survival
Computational Biology
Neoplasms
Proteins
Transcription Factors
Growth
Hypoxia

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Airley, R. E. ; McHugh, P. ; Evans, A. R. ; Harris, B. ; Winchester, L. ; Buffa, F. M. ; Al-Tameemi, W. ; Leek, R. ; Harris, A. L. / Role of carbohydrate response element-binding protein (ChREBP) in generating an aerobic metabolic phenotype and in breast cancer progression. In: British Journal of Cancer. 2014 ; Vol. 110, No. 3. pp. 715-723.
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Role of carbohydrate response element-binding protein (ChREBP) in generating an aerobic metabolic phenotype and in breast cancer progression. / Airley, R. E.; McHugh, P.; Evans, A. R.; Harris, B.; Winchester, L.; Buffa, F. M.; Al-Tameemi, W.; Leek, R.; Harris, A. L.

In: British Journal of Cancer, Vol. 110, No. 3, 04.02.2014, p. 715-723.

Research output: Contribution to journalArticle

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AU - Airley, R. E.

AU - McHugh, P.

AU - Evans, A. R.

AU - Harris, B.

AU - Winchester, L.

AU - Buffa, F. M.

AU - Al-Tameemi, W.

AU - Leek, R.

AU - Harris, A. L.

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N2 - 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.

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