DIFFERENTIAL EXPRESSION IN GLIOBLASTOMA-MULTIFORME AND CEREBRAL HEMANGIOBLASTOMA OF CYTOPLASMIC PROTEINS THAT BIND 2 DIFFERENT DOMAINS WITHIN THE 3'-UNTRANSLATED REGION OF THE HUMAN GLUCOSE-TRANSPORTER-1 (GLUT1) MESSENGER-RNA

The glucose transporter 1 (GLUT1) protein is underexpressed in human g lioblastoma multiforme and is overexpressed in human cerebral hemangio blastoma, To gain insight into possible posttranscriptional mechanisms regulating the expression of the GLUT1 protein in human brain tumors, cytosolic proteins were prepared from these two tumors and used in RN ase T1 protection assays that employed [P-32]human GLUT1 synthetic RNA prepared from transcription plasmids. Gel shift mobility assays and u ltraviolet light cross-linking studies demonstrated the formation of s pecific RNA/protein complexes that migrated with a mol mass of 120, 44 , and 41 kD, RNase T1 mapping and oligodeoxynucleotide competition stu dies showed that the 120 kD complex was comprised of an RNA fragment t hat localized to nucleotides 2186-2203 of the GLUT1 mRNA, The 44 kD co mplex contained an adenosine-uridine-rich RNA fragment that localized to nucleotides 1885-1906 of the human GLUT1 mRNA, and the formation of this complex was inhibited by synthetic RNA enriched in adenosine-uri dine sequences, The 44 kD complex was selectively downregulated in hem angioblastoma as compared to glioblastoma multiforme. These studies de monstrate that human brain tumors have differential regulation of cyto solic proteins that specifically interact with two different domains i n the 3'-untranslated region of the GLUT1 mRNA, which may serve to med iate the posttranscriptional regulation of GLUT1 gene expression in th ese tumors.