Biotechnologia Acta

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ISSN 1995-5537

Scientific journal

БІОТЕХНОЛОГІЯ

V. 1, No. 4, 2008


"Biotechnology" journal Vol. 1, No. 4, 2008
Р. 49-56, Bibliography 47, English.
Universal Decimal classification 577.112:616

 

Palladin Institute of Biochemistry of National Academy of Science of Ukraine, Kyiv
Research Center for Innovative Oncology of National Cancer Center Hospital East,
Kashiwa, Japan
INSERM U920 Molecular Mechanisms of Angiogenesis Laboratory,
University Bordeaux 1, Talence, France
Department of Medicine,
Jefferson Medical College of Thomas Jefferson University, Philadelphia, PA, USA
Expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB), a key regulatory enzyme of glycolysis, is significantly increased in different malignant tumors provides a potential mechanism of enhanced glycolysis and cancer cell proliferation.

We created dominant-negative constructs of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 and -4 (dnPFKFB-3 and dnPFKFB-4) cDNA for suppression of strongly enhanced expression endogenous PFKFB-3 and PFKFB-4. We introduce point mutation in ATP-binding domain of 6-phosphofructo-2-kinase part of PFKFB-3 as well as PFKFB-4 cDNA for suppression of 6-phosphofructo-2-kinase activity in the products of dnPFKFB-3 and dnPFKFB-4 expression.

Cancer cells were stable transfected with these dominant-negative constructs for suppression of endogenous PFKFB-3 and PFKFB-4 expression and cell proliferation. We have shown that PFKFB-3 expression in pancreatic cancer cell line Panc1, stable transfected by dnPFKFB-3, was significantly reduced in normal as well as in hypoxic conditions. Pancreatic cancer cells proliferation, stable transfected by dnPFKFB-3 or dnPFKFB-4, was also reduced. Results of this investigation demonstrate possibility to apply the dominant-negative constructs of PFKFB-3 and PFKFB-4 for suppression of glycolysis and tumor cells proliferation via reduction of endogenous PFKFB expression.
Key words: PFKFB4 mRNA, PFKFB3 mRNA, dominantnegative constructs, cancer cells.

© Palladin Institute of Biochemistry of National Academy of Sciences of Ukraine, 2008

 

 

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© Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine, 2008.
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