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Glioblastoma Cell-specific Expression of Fibroblast Growth Factor Receptor-1ß Requires an Intronic Repressor of RNA Splicing¹

Section of Endocrine Neoplasia and Hormonal Disorders, Department of Medical Specialties, The University of Texas, M. D. Anderson Cancer Center, Houston, Texas 77030

The fibroblast growth factor receptor-1 (FGFR-1) primary transcript is alternatively processed to produce receptors that vary in their ligand affinity and specificity. A high affinity form of this receptor—FGFR-1ß—that lacks the exon is observed on the neoplastic transformation of glial cells. In this study, we have identified a 62-bp sequence located 97 bp downstream from the exon that is required for the exclusion of this exon in a human glioblastoma cell line. Deletion or mutation of this sequence is sufficient to allow enhanced inclusion of the exon or a heterologous exon in glioblastoma cells. Therefore, it would appear that this sequence element plays a key role in the glioblastoma-specific splicing to form FGFR-1ß mRNA.

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