Fibroblast growth factor receptor-1 alpha-exon exclusion and polypyrimidine tract-binding protein in glioblastoma multiforme tumors.
Neoplastic transformation of glial cells alters inclusion of the alpha exon in human fibroblast growth factor receptor-1 (FGFR-1) mRNA transcripts. Although normal cells predominantly include the alpha exon, this exon is excluded in most glioblastoma cell transcripts, creating a high-affinity receptor form. In this study, we identified polypyrimidine tract-binding protein (PTB) as a regulator of FGFR-1 splicing. PTB interacted in a sequence-specific manner with the ISS-1 regulatory element in the intron upstream of the a exon. PTB expression was also strongly increased in seven malignant glioblastoma multiforme tumors relative to adjacent normal tissue, but not in a low-grade astrocytoma. These results suggest that increased expression of PTB may contribute to glial cell malignancy.
Jin
W
W
Department of Medical Specialties, The University of Texas, M.D. Anderson Cancer Center, Houston 77030, USA.
McCutcheon
I E
IE
Fuller
G N
GN
Huang
E S
ES
Cote
G J
GJ
D002471:Cell Transformation, Neoplastic / Q000235:genetics; D005091:Exons; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D038941:Polypyrimidine Tract-Binding Protein; D016601:RNA-Binding Proteins / Q000235:genetics*; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics*; D012261:Ribonucleoproteins / Q000235:genetics*; D014407:Tumor Cells, Cultured
D016601:RNA-Binding Proteins; D017468:Receptors, Fibroblast Growth Factor; D012261:Ribonucleoproteins; D038941:Polypyrimidine Tract-Binding Protein