Overexpression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-4 in the human breast and colon malignant tumors.
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.
Minchenko
O H
OH
Department of Molecular Biology, Palladin Institute of Biochemistry National Academy of Science of Ukraine, Kyiv 01601, Ukraine. ominchenko@yahoo.com
Ochiai
A
A
Opentanova
I L
IL
Ogura
T
T
Minchenko
D O
DO
Caro
J
J
Komisarenko
S V
SV
Esumi
H
H
D001940:Breast / Q000201:enzymology; D001943:Breast Neoplasms / Q000201:enzymology*; D003106:Colon / Q000201:enzymology; D003110:Colonic Neoplasms / Q000201:enzymology*; D051272:Glucose Transporter Type 1 / Q000096:biosynthesis; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis; D007527:Isoenzymes / Q000096:biosynthesis*; D025481:Phosphofructokinase-2 / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
D051272:Glucose Transporter Type 1; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007527:Isoenzymes; C506672:PFKFB4 protein, human; C495677:SLC2A1 protein, human; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C107345:PFKFB3 protein, human; D025481:Phosphofructokinase-2