Visit our Expo - Redox and Inflammation signaling 2012

Session XIV : Transcriptional and translational control Poster XIV, 40
Differential regulation of vascular endothelial growth factor expression by peroxisome
proliferator-activated receptors via adipocyte-fatty acid binding protein in bladder
cancer cells
Isabelle Lascombe, Guillaume Boiteux, Hugues Bittard and Sylvie Fauconnet
Université de Franche-Comté, EA 3181 “Carcinogenèse épithéliale”, IFR133, UFR
Médecine et Pharmacie, 19 rue Ambroise Paré, 25000 Besançon, France. E-mail :
isabelle.lascombe@voila.fr
Vascular endothelial growth factor (VEGF) plays a prominent role in vesical tumor
angiogenesis regulation (Lascombe et al., 2005, PBCR review). Peroxisome proliferatoractivated
receptors (PPAR), which are transcription factors, are involved in angiogenesis
process. Recently, we reported for the first time that, in two different human bladder cancer
cell lines RT4 (derived from grade I tumor) and T24 (derived from grade III tumor), VEGF is
differentially up-regulated by the three PPAR isotypes. Its expression is increased by
PPARalpha, # and in RT4 cells and only by PPAR# in T24 cells via a transcriptional
activation of the VEGF promoter through an indirect mechanism (Fauconnet et al., J Biol
Chem, 2002). Our purpose was to elucidate the molecular mechanism involved in PPARinduced
VEGF expression. We hypothesized that in high grade T24 cells, the inactivity of
PPARalpha and $ could be due to the absence of adipocyte-fatty acid binding protein (A-
FABP) expression or to the loss of the protein functionality. Indeed, loss of A-FABP is
associated with progression in bladder transitional cell carcinomas. Furthermore, recent
studies establish that FABP govern the transcriptional activities of their ligands by targeting
them to PPAR in the nucleus, thereby enabling PPAR to exert their biological functions. Our
first results suggest that A-FABP is present in cytoplasm of both RT4 and T24 cells but does
not locate to the nucleus of the T24 cells. Preliminary data obtained with siRNA targeting A-
FABP seem to confirm the role of this protein in PPAR-induced VEGF expression. These
data contribute to a better understanding of the mechanisms by which PPARs regulate VEGF
expression in non aggressive bladder tumors. This could lead to a new therapeutic approach
for human bladder cancer in which excessive angiogenesis is a negative prognostic factor.
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