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-Exon Exclusion and Polypyrimidine Tract-binding Protein in Glioblastoma Multiforme Tumors1
Departments of Medical Specialties [W. J., E. S-C. H., G. J. C.], Neurosurgery [I. E. M.], and Pathology [G. N. F.], The University of Texas, M. D. Anderson Cancer Center, Houston, Texas 77030
Neoplastictransformation of glial cells alters inclusion of the 
exon in human
fibroblast growth factor receptor-1 (FGFR-1) mRNA transcripts. Although
normal cells predominantly include the 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 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.
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