title: Role of carbohydrate response element-binding protein (ChREBP) in generating an aerobic metabolic phenotype and in breast cancer progression.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Pharmacy, University of Huddersfield, Huddersfield HD1 3DH, UK.
authors.forename: R E
authors.initials: RE
authors.lastname: Airley
authors.affiliation: Division of Pharmacy, University of Huddersfield, Huddersfield HD1 3DH, UK.
authors.forename: P
authors.initials: P
authors.lastname: McHugh
authors.affiliation: School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool L3 3AF, UK.
authors.forename: A R
authors.initials: AR
authors.lastname: Evans
authors.affiliation: Department of Oncology, Weatherall Institute for Molecular Medicine, University of Oxford, Oxford OX3 7DQ, UK.
authors.forename: B
authors.initials: B
authors.lastname: Harris
authors.affiliation: Department of Oncology, Weatherall Institute for Molecular Medicine, University of Oxford, Oxford OX3 7DQ, UK.
authors.forename: L
authors.initials: L
authors.lastname: Winchester
authors.affiliation: Department of Oncology, Weatherall Institute for Molecular Medicine, University of Oxford, Oxford OX3 7DQ, UK.
authors.forename: F M
authors.initials: FM
authors.lastname: Buffa
authors.affiliation: Division of Pharmacy, University of Huddersfield, Huddersfield HD1 3DH, UK.
authors.forename: W
authors.initials: W
authors.lastname: Al-Tameemi
authors.affiliation: Nuffield Department of Clinical Laboratory Science, University of Oxford, Oxford OX3 7DQ, UK.
authors.forename: R
authors.initials: R
authors.lastname: Leek
authors.affiliation: Department of Oncology, Weatherall Institute for Molecular Medicine, University of Oxford, Oxford OX3 7DQ, UK.
authors.forename: A L
authors.initials: AL
authors.lastname: Harris
mesh_terms: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D051272:Glucose Transporter Type 1 / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D000860:Hypoxia / Q000235:genetics* / Q000473:pathology; D007150:Immunohistochemistry; D061986:MCF-7 Cells; D011379:Prognosis
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D014408:Biomarkers, Tumor; D051272:Glucose Transporter Type 1; C116385:MLXIPL protein, human