Expression and hypoxia-responsiveness of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4 in mammary gland malignant cell lines.

摘要: Recently, we have shown that PFKFB4 gene which encodes the testis isoenzyme of PFKFB is also expressed in prostate and hepatoma cancer cell lines. Here studied expression hypoxic regulation several malignant lines from a female organ--the mammary gland. Our studies clearly demonstrated mRNA gland cells (MCF-7 T47D lines) normoxic conditions hypoxia strongly induces it expression. To better understand mechanism expression, used dimethyloxalylglycine, specific inhibitor HIF-1alpha hydroxylase enzymes, increases levels mimics effect hypoxia. It was observed MCF7 highly responsive to suggesting responsiveness these regulated by HIF-1 proteins. Moreover, desferrioxamine cobalt chloride, mimic chelating or substituting for iron, had similar stimulatory on mRNA. In other (BT549, MDA-MB-468, SKBR-3) induced mRNA, but variable degrees. The induction equivalent PFKFB3, Glut1, VEGF, are known HIF-1-dependent genes. Hypoxia dimethyloxalylglycine increased protein all except MDA-MB-468. Through site-specific mutagenesis 5'-flanking region response could be limited. Thus, this study provides evidence responds via an dependent mechanism. PFKFB3 has significant role Warburg found cells.