Overexpression of high molecular weight FGF-2 forms inhibits glioma growth by acting on cell-cycle progression and protein translation

Sylvie Lemiere, Rania Azar, Francis Belloc, Demir Gürsel, Stéphane Pyronnet, Andreas Bikfalvi*, Patrick Auguste

*Corresponding author for this work

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

In order to clarify the role of HMW FGF-2 in glioma development and angiogenesis, we over-expressed different human FGF-2 isoforms in C6 rat glioma cell line using a tetracycline-regulated expression system. Phenotypic modifications were analyzed in vitro and compared to untransfected cells or to cells over-expressing 18 kDa FGF-2 or all FGF-2 isoforms. In particular, we demonstrate that HMW FGF-2 has unique features in inhibiting glioma cell proliferation. HMW FGF-2 expressing cells showed a cell-cycle arrest at the G2M, demonstrating a role of HMW FGF-2 in controlling the entry in mitosis. Moreover, hydroxyurea was ineffective in blocking cells at the G1S boundary when HMW FGF-2 was expressed. We also show that the HMW FGF-2 isoforms inhibit 4E-BP1 phosphorylation at critical sites restoring the translation inhibitory activity of 4E-BP1. In vivo, inhibition of tumor growth was observed when cells expressed HMW FGF-2. This indicates that HMW FGF-2 inhibits tumor growth in glioma cells by acting on cell-cycle progression and protein translation.

Original languageEnglish (US)
Pages (from-to)3701-3711
Number of pages11
JournalExperimental Cell Research
Volume314
Issue number20
DOIs
StatePublished - Dec 10 2008

Keywords

  • Fibroblast growth factors
  • Glioma
  • Invasion

ASJC Scopus subject areas

  • Cell Biology

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