Overexpression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-4 in the human breast and colon malignant tumors

Biochimie. 2005 Nov;87(11):1005-10. doi: 10.1016/j.biochi.2005.04.007.

Abstract

6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB) is a bifunctional enzyme, which is responsible for maintaining the cellular level of fructose-2,6-bisphosphate, a powerful allosteric activator of glycolysis. We describe herein the overexpression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-4 (PFKFB-4) isozyme in the human breast and colon malignant tumors as compared to corresponding non-malignant tissue counterparts. We have shown also that breast malignant cell line MCF7 constitutively express PFKFB-4 mRNA and that the expression of this gene is highly induced by hypoxia. Overexpression of PFKFB-4 transcript levels in breast and colon malignant tumors correlates with enhanced expression of PFKFB-3, hypoxia-inducible factor (HIF)-1alpha and known HIF-1 dependent genes glucose transporter 1 (Glut1) and vascular endothelial growth factor (VEGF). Thus, our data clearly demonstrates overexpression of PFKFB-4 mRNA and protein in the breast and colon malignant tumors.

MeSH terms

  • Breast / enzymology
  • Breast Neoplasms / enzymology*
  • Colon / enzymology
  • Colonic Neoplasms / enzymology*
  • Glucose Transporter Type 1 / biosynthesis
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / biosynthesis
  • Isoenzymes / biosynthesis*
  • Phosphofructokinase-2 / biosynthesis*
  • Tumor Cells, Cultured
  • Vascular Endothelial Growth Factor A / biosynthesis

Substances

  • Glucose Transporter Type 1
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Isoenzymes
  • PFKFB4 protein, human
  • SLC2A1 protein, human
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • PFKFB3 protein, human
  • Phosphofructokinase-2