Glut-1 and hexokinase expression: Relationship with 2-fluoro-2-deoxy-D-glucose uptake in A431 and T47D cells in culture

Uptake of 2-[F-18]-2-deoxy-D-glucose (FDG) has been used as a marker of inc reased glucose metabolism to visualize, stage, and monitor progression of h uman cancers with positron emission tomography. Many human tumors have been shown to overexpress the Glut-1 glucose transport protein. The aim of this study is to define whether a quantitative relationship exists between the amount of Glut-1 expressed by cells and their ability to accumulate FDG, We characterized the expression of the known facilitative and sodium-dependen t glucose transporter isoforms in six different cancer cell lines used in o ur laboratory (A431, MDA-MB-231, T47D, CaCo II, MCF7, and HepG2). A431 and T47D cells express, respectively, the highest and lowest amount of Glut-1 m RNA by Northern blot of all of the cells analyzed, and no other glucose tra nsporter isoforms were detectable by this method in both cell lines. Both t otal and plasma membrane-associated Glut-1 protein levels were higher in A4 31 than in T47D cells, consistent with the higher Glut-1 mRNA levels. Howev er, T47D cells accumulate FDG more rapidly than do A431 cells. 3-O-Methylgl ucose transport is higher in A431 cells. Although hexokinase I and II mRNA levels are higher in A431 cells than in T47D cells, the ability of mitochon drial preparations to phosphorylate FDG is higher in T47D cells, Our data i ndicate that in these cultured cells, FDG uptake correlates better with FDG phosphorylating activity of mitochondrial preparations rather than the lev el of expression of the Glut-1 or hexokinase I and ZI genes.