Glycolytic phenotype in breast cancer: activation of Akt, up-regulation of GLUT1, TKTL1 and down-regulation of M2PK

J Cancer Res Clin Oncol. 2010 Feb;136(2):219-25. doi: 10.1007/s00432-009-0652-y. Epub 2009 Aug 5.

Abstract

Purpose: Metabolic dependence on glucose utilisation has been described for different tumours characterised by activation of Akt, upregulation of GLUT1, M2PK and TKTL1. To date, however, little is known about glucose metabolism in breast cancer tissue.

Methods: We analysed 55 breast cancer specimens, 26 adjacent ductal carcinomas in situ (DCIS) and 23 adjacent normal breast tissues for expression of glycolytic markers by immunohistochemistry.

Results: We found expression of pAkt in 49%, GLUT1 in 25%, M2PK in 68% and TKTL1 in 31% of the tumours investigated. Expression of pAkt and Her2neu are positively correlated with borderline significance (P = 0.055). Expression of pAkt, GLUT1 and TKTL1 were higher in breast cancer and DCIS than in normal tissue. Surprisingly, M2PK expression was highest in normal breast tissue.

Conclusions: We found a glycolytic phenotype in a high percentage of breast cancer samples. Inhibition of glycolysis might evolve as a future option for breast cancer therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Breast / metabolism
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Carcinoma / metabolism
  • Carcinoma / pathology
  • Carcinoma, Intraductal, Noninfiltrating / metabolism
  • Carcinoma, Intraductal, Noninfiltrating / pathology
  • Dimerization
  • Female
  • Gene Expression Regulation, Neoplastic
  • Glucose Transporter Type 1 / genetics
  • Glucose Transporter Type 1 / metabolism*
  • Glycolysis* / genetics
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen / metabolism
  • Lymphatic Metastasis
  • Phenotype
  • Prognosis
  • Proto-Oncogene Proteins c-akt / genetics*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Pyruvate Kinase / genetics
  • Pyruvate Kinase / metabolism*
  • Receptor, ErbB-2 / metabolism
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / metabolism
  • Transcriptional Activation
  • Transketolase / genetics
  • Transketolase / metabolism*
  • Up-Regulation

Substances

  • Biomarkers, Tumor
  • Glucose Transporter Type 1
  • Ki-67 Antigen
  • Receptors, Estrogen
  • Receptors, Progesterone
  • SLC2A1 protein, human
  • TKTL1 protein, human
  • Transketolase
  • Pyruvate Kinase
  • Receptor, ErbB-2
  • Proto-Oncogene Proteins c-akt