Journal
EXPERIMENTAL CELL RESEARCH
Volume 314, Issue 20, Pages 3701-3711Publisher
ELSEVIER INC
DOI: 10.1016/j.yexcr.2008.09.022
Keywords
Fibroblast growth factors; Glioma; Invasion
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Funding
- Institut National du Cancer, (INCA)
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In order to clarify the role of HMW FGF-2 in glioma development and angiogenesis, we overexpressed 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. (c) 2008 Elsevier Inc. All rights reserved.
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