Basic fibroblast growth factor and fibroblast growth factor receptor I are implicated in the growth of human astrocytomas

Richard S. Morrison, Fumio Yamaguchi, Hideyuki Saya, Janet M. Bruner, Alan M. Yahanda, Lawrence A. Donehower, Mitchel Berger

Research output: Contribution to journalArticle

96 Citations (Scopus)

Abstract

Malignant astrocytomas are highly invasive, vascular neoplasms that comprise the majority of nervous system tumors in humans. A strong association has previously been made between malignancy in human astrocytic tumors and increased expression of certain fibroblast growth factor (FGF) family members, including basic and acidic FGF. The influence of endogenous basic FGF on glioblastoma cell growth in vitro was evaluated using basic FGF-specific antisense oligonucleotides. These studies indicated that human glioblastoma cell growth in vitro, can be inhibited by suppressing basic FGF expression. Human astrocytomas also exhibited changes in FGF receptor (FGFR) expression during the course of their progression from a benign to a malignant phenotype. FGFR2 (bek) expression was abundant in normal white matter and in all low grade astrocytomas, but was not observed in glioblastomas. Conversely, FGFR1 (flg) expression was absent or barely detectable in normal white matter, but was significantly elevated in glioblastomas. Glioblastomas also expressed an alternatively spliced form of FGFR1 containing two immunoglobulin-like disulfide loops (FGFR1β), whereas normal human adult and fetal brain expressed a form of the receptor containing three immunoglobulin-like disulfide loops (FGFR1α). Intermediate grades of astrocytic tumors exhibited a gradual loss of FGFR2 and a shift in expression from FGFR1α to FGFR1β as they progressed from a benigh to a malignant phenotype. The underlying cytogenetic changes that contribute to these alterations are not entirely understood, but abnormalities in the p53 tumor suppressor gene may influence expression of bFGF as well as the FGFR. These results suggest that alterations in FGFR signal transduction pathways may play a critical role in the malignant progression of astrocytic tumors.

Original languageEnglish
Pages (from-to)207-216
Number of pages10
JournalJournal of Neuro-Oncology
Volume18
Issue number3
DOIs
Publication statusPublished - 1994 Oct
Externally publishedYes

Fingerprint

Fibroblast Growth Factor Receptors
Astrocytoma
Fibroblast Growth Factor 2
Glioblastoma
Growth
Disulfides
Immunoglobulins
Neoplasms
Vascular Neoplasms
Nervous System Neoplasms
Phenotype
Fibroblast Growth Factor 1
Fibroblast Growth Factors
Antisense Oligonucleotides
Tumor Suppressor Genes
Cytogenetics
Signal Transduction
Brain

Keywords

  • angiogenesis
  • astrocytoma
  • brain tumor
  • central nervous system
  • glioma
  • malignant progression

ASJC Scopus subject areas

  • Neuroscience(all)
  • Oncology
  • Clinical Neurology
  • Cancer Research

Cite this

Basic fibroblast growth factor and fibroblast growth factor receptor I are implicated in the growth of human astrocytomas. / Morrison, Richard S.; Yamaguchi, Fumio; Saya, Hideyuki; Bruner, Janet M.; Yahanda, Alan M.; Donehower, Lawrence A.; Berger, Mitchel.

In: Journal of Neuro-Oncology, Vol. 18, No. 3, 10.1994, p. 207-216.

Research output: Contribution to journalArticle

Morrison, Richard S. ; Yamaguchi, Fumio ; Saya, Hideyuki ; Bruner, Janet M. ; Yahanda, Alan M. ; Donehower, Lawrence A. ; Berger, Mitchel. / Basic fibroblast growth factor and fibroblast growth factor receptor I are implicated in the growth of human astrocytomas. In: Journal of Neuro-Oncology. 1994 ; Vol. 18, No. 3. pp. 207-216.
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