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

  • Melanie SchmidtEmail author
  • Hans-Ullrich Voelker
  • Michaela Kapp
  • Mathias Krockenberger
  • Johannes Dietl
  • Ulrike Kammerer
Original Paper



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.


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.


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.


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.


Breast cancer Akt GLUT1 M2PK TKTL1 



We thank André Schmidt and Kurt Weigand for their valuable discussions, Marianne Florey for critical review of the manuscript, as well as Tanja Kottmann for statistical analysis. This study was supported by the Medical Faculty of the University of Wuerzburg and “Hilfe im Kampf gegen Krebs e.V.”

Conflict of Interest Statement

We declare that we have no conflict of interest.


  1. Barnes K, McIntosh E, Whetton AD et al (2005) Chronic myeloid leukaemia: an investigation into the role of Bcr-Abl-induced abnormalities in glucose transport regulation. Oncogene 24:3257–3267. doi: 10.1038/sj.onc.1208461 CrossRefPubMedGoogle Scholar
  2. Buzzai M, Bauer DE, Jones RG et al (2005) The glucose dependence of Akt-transformed cells can be reversed by pharmacologic activation of fatty acid beta-oxidation. Oncogene 24:4165–4173. doi: 10.1038/sj.onc.1208622 CrossRefPubMedGoogle Scholar
  3. Comin-Anduix B, Boren J, Martinez S et al (2001) The effect of thiamine supplementation on tumour proliferation. A metabolic control analysis study. Eur J Biochem 268:4177–4182. doi: 10.1046/j.1432-1327.2001.02329.x CrossRefPubMedGoogle Scholar
  4. Coy JF, Dressler D, Wilde J et al (2005) Mutations in the transketolase-like gene TKTL1: clinical implications for neurodegenerative diseases, diabetes and cancer. Clin Lab (Zaragoza) 51:257–273Google Scholar
  5. Cross DA, Alessi DR, Cohen P et al (1995) Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B. Nature 378:785–789. doi: 10.1038/378785a0 CrossRefPubMedGoogle Scholar
  6. Hatanaka Y, Hashizume K, Kamihara Y et al (2001) Quantitative immunohistochemical evaluation of HER2/neu expression with HercepTestTM in breast carcinoma by image analysis. Pathol Int 51:33–36. doi: 10.1046/j.1440-1827.2001.01162.x CrossRefPubMedGoogle Scholar
  7. Krockenberger M, Honig A, Rieger L et al (2007) Transketolase-like 1 (TKTL1) expression correlates with subtypes of ovarian cancer and the presence of distant metastases. Int J Gynecol Cancer 17:101–106. doi: 10.1111/j.1525-1438.2007.00799.x CrossRefPubMedGoogle Scholar
  8. Langbein S, Zerilli M, Zur Hausen A et al (2006) Expression of transketolase TKTL1 predicts colon and urothelial cancer patient survival: Warburg effect reinterpreted. Br J Cancer 94:578–585. doi: 10.1038/sj.bjc.6602962 CrossRefPubMedGoogle Scholar
  9. Lee WN, Boros LG, Puigjaner J et al (1998) Mass isotopomer study of the nonoxidative pathways of the pentose cycle with [1, 2–13C2]glucose. Am J Physiol 274:843–851Google Scholar
  10. Mazurek S, Boschek CB, Hugo F et al (2005) Pyruvate kinase type M2 and its role in tumor growth and spreading. Semin Cancer Biol 15:300–308. doi: 10.1016/j.semcancer.2005.04.009 CrossRefPubMedGoogle Scholar
  11. Pelicano H, Martin DS, Xu RH et al (2006) Glycolysis inhibition for anticancer treatment. Oncogene 25:4633–4646. doi: 10.1038/sj.onc.1209597 CrossRefPubMedGoogle Scholar
  12. Rathmell JC, Fox CJ, Plas DR et al (2003) Akt-directed glucose metabolism can prevent Bax conformation change and promote growth factor-independent survival. Mol Cell Biol 23:7315–7328. doi: 10.1128/MCB.23.20.7315-7328.2003 CrossRefPubMedGoogle Scholar
  13. Remmele W, Stegner HE (1987) Recommendation for uniform definition of an immunoreactive score (IRS) for immunohistochemical estrogen receptor detection (ER-ICA) in breast cancer tissue. Pathologe 8:138–140PubMedGoogle Scholar
  14. Schmidt M, Kammerer U, Segerer S et al (2008) Glucose metabolism and angiogenesis in granulosa cell tumors of the ovary: activation of Akt, expression of M2PK, TKTL1 and VEGF. Eur J Obstet Gynecol Reprod Biol 139:72–78. doi: 10.1016/j.ejogrb.2008.02.009 CrossRefPubMedGoogle Scholar
  15. Schneider J, Neu K, Velcovsky HG et al (2003) Tumor M2-pyruvate kinase in the follow-up of inoperable lung cancer patients: a pilot study. Cancer Lett 193:91–98. doi: 10.1016/S0304-3835(02)00720-6 CrossRefPubMedGoogle Scholar
  16. Singletary SE, Connolly JL (2006) Breast cancer staging: working with the sixth edition of the AJCC Cancer Staging Manual. CA Cancer J Clin 56:37–47. doi: 10.3322/canjclin.56.1.37 CrossRefPubMedGoogle Scholar
  17. Slamon DJ, Clark GM, Wong SG et al (1987) Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235:177–182. doi: 10.1126/science.3798106 CrossRefPubMedGoogle Scholar
  18. Sternlicht MD, Kedeshian P, Shao ZM et al (1997) The human myoepithelial cell is a natural tumor suppressor. Clin Cancer Res 3:1949–1958PubMedGoogle Scholar
  19. Sun M, Wang G, Paciga JE et al (2001) AKT1/PKBalpha kinase is frequently elevated in human cancers and its constitutive activation is required for oncogenic transformation in NIH3T3 cells. Am J Pathol 159:431–437PubMedGoogle Scholar
  20. Warburg O (1924) Über den Stoffwechsel der Carcinomzelle. Naturwissenschaften 50:1131–1137. doi: 10.1007/BF01504608 CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Melanie Schmidt
    • 1
    Email author
  • Hans-Ullrich Voelker
    • 2
  • Michaela Kapp
    • 1
  • Mathias Krockenberger
    • 1
  • Johannes Dietl
    • 1
  • Ulrike Kammerer
    • 1
  1. 1.Department of Gynaecology and ObstetricsUniversity of WuerzburgWuerzburgGermany
  2. 2.Department of PathologyUniversity of WuerzburgWuerzburgGermany

Personalised recommendations