Visit our Expo - Redox and Inflammation signaling 2012

Session X : Cell death in cancer Poster X, 14
Endogenous FGF1 inhibits p53-dependent apoptosis
Sylvina Bouleau, Vincent Rincheval, Bernard Mignotte, Jean-Luc Vayssière, Flore
Renaud.
Laboratoire de Génétique et Biologie Cellulaire, CNRS FRE2445, Ecole Pratique des
Hautes Etudes, Université de Versailles, 45 Av des Etats Unis, 78035 Versailles, France.
E-mail : bouleau@genetique.uvsq.fr
The oncosuppressor p53 is an important regulator of apoptosis and is associated with few
diseases (like cancers, neurodegenerative diseases…). In contrast to p53, survival factors
inhibit the cell death process. Their action is usually mediated via paracrine and/or autocrine
pathways. However, some survival factors, as FGF1 and FGF2, do not contain secretion
peptide signal but a nuclear localization signal (NLS) and may act via an intracrine pathway.
We have initiated the study of the role of FGF1 in p53-dependent apoptosis in a rat embryo
fibroblast cellular model. We have shown that : (1) p53 represses fgf1 gene expression; (2)
FGF1 overexpression inhibits pro-apoptotic and anti-proliferative p53 activities via an
intracrine pathway; (3) FGF1 increases the level of MDM2, which induced p53 degradation;
(4) FGF1 inhibits the p53-dependent trans-activation of the bax gene, which code a major
pro-apoptotic protein (Bouleau S. et al. , 2005, Oncogene, 24(53) : 7839-7849).
Then, we persue this study in a neuronal cellular model: the PC12 cells (issued from a rat
pheocromocytoma). These cells can differentiate in sympathetic like neurons in presence of
neurotrophic factors like NGF or FGF1. First, we have characterized the apoptosis process
induced by etoposide, to ascertain the implication of p53 in this process. Second, we have
shown that the addition of recombinant FGF1 in the culture medium protects the cells from
p53-dependent cell death, suggesting a protective activity of exogenous FGF1. Actually, we
initiate the study of the activity of endogenous FGF1. In particular, we currently analyze the
activity of intracellular and nuclear FGF1 on p53-dependent apoptosis.
Bouleau S, Grimal H, Rincheval V, Godefroy N, Mignotte B, Vayssière JL, Renaud F. “FGF1
inhibits p53-dependent apoptosis and cell cycle arrest via an intracrine pathway”. 2005,
Oncogene, 24(53) : 7839-7849.
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