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

Sylvie Lemiere (1) , Rania Azar (2) , Francis Belloc (3, 4) , Demir Gürsel (1) , Stéphane Pyronnet (2) , Andreas Bikfalvi (1) , Patrick Auguste (1)

1 Mécanismes moléculaires de l'angiogénèse
2 I2MR - Institut de médecine moléculaire de Rangueil
3 Transfert de gènes à visée thérapeutique dans les cellules souches
4 Hôpital Haut-Lévêque

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.

Domaines: Biochimie, Biologie Moléculaire

Sylvie Lemiere, Rania Azar, Francis Belloc, Demir Gürsel, Stéphane Pyronnet, et al.. Overexpression of high molecular weight FGF-2 forms inhibits glioma growth by acting on cell-cycle progression and protein translation.. Experimental Cell Research, 2008, 314 (20), pp.3701-11. ⟨10.1016/j.yexcr.2008.09.022⟩. ⟨inserm-00409173⟩