Minchenko D. Expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase in malignant tumor cells: molecular mechanisms of regulation.

Investigation object - expression of pfkfb3, pfkfb4, hif1 , hif2 , vegf and glut1 in different malignant tumors and cancer cell lines. The aim - identification of changes in the expression of different isoforms of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase, HIF- and some HIF-dependent genes in the lung, breast and colon cancers, identification of molecular mechanisms of PFKFB-4 transcription regulation under hypoxia in different cancer cell lines as well as identification of PFKFB-4 mRNA splice variants. The methods - biochemical and molecular biological. Novelty of investigation - for the first time was shown that pfkfb2, pfkfb3, pfkfb4, hif1 , vegf and glut1 gene expression significantly increased in different malignant tumors; that pfkfb4 gene expression significantly increased in different cancer cell lines under hypoxia via specific interaction of HIF transcription factor with hypoxia responsive element in 5'-regulatory region of pfkfb4 gene; we identified three new unique alternative splice variants of PFKFB-4 mRNA in cancer cells and normal tissues as well as its sequence and role of alternative splicing in glycolysis regulation. Degree of application - results of this investigation are applied in education process in biochemistry department of Taras Schevchenko Kyiv National University and used in research work of molecular biology department of Palladin Institute of Biochemistry. The field is biochemistry.