[Inhibition of fibroblast growth factor receptor 1 expression in human glioblastoma cell contributes to the cell growth suppression].
Although normal human astrocytes rarely express fibroblast growth factor receptor 1 (FGFR 1) mRNA, expression of FGFR 1 mRNA in astrocytomas increases as malignancy progresses. This result suggests that FGFR 1 can be one of important factors for glioblastoma cell growth. In our study, specific antisense oligonucleotides for FGFR 1 mRNA inhibited cell growth of SNB 19, human glioblastoma cell line, while sense oligonucleotides showed no cell reduction. And Southern blot analysis demonstrated decreased expression of FGFR 1 mRNA in only antisense group. Furthermore, cross-linking analysis revealed decreased number of FGFR 1 in antisense-treated SNB 19 in protein level. These results conclude that cell growth inhibition was caused by suppression of both transcription and translation of FGFR 1 mRNA. Interestingly, alpha-specific antisense also inhibited expression of beta-, and gamma-type of FGFR 1 mRNA which had no binding sites for the oligonucleotides. This fact indicates that antisense oligonucleotides binds to premature mRNA, which is previous form of mature mRNA before splicing, in nucleus. It is previously reported that basic fibroblast growth factor (bFGF), major ligand to FGFR 1, was overly expressed in human malignant astrocytomas. Thus, increased number of FGFR 1 may contribute to the acceleration of bFGF autocrine or paracrine mechanism in glioblastoma.
Yamada
S M
SM
Department of Neurosurgery, Nippon Medical School, Tokyo, Japan.
Yamaguchi
F
F
Morrison
R S
RS
Takahashi
H
H
Teramoto
A
A
D001932:Brain Neoplasms / Q000473:pathology*; D002455:Cell Division / Q000502:physiology; D005909:Glioblastoma / Q000473:pathology*; D006801:Humans; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D051496:Receptor, Fibroblast Growth Factor, Type 1; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured