EGR1 expression: a calcium and ERK1/2 mediated PPARgamma-independent event involved in the antiproliferative effect of 15-deoxy-Delta12,14-prostaglandin J2 and thiazolidinediones in breast cancer cells.
Fiche publication
Date publication
mai 2011
Auteurs
Membres identifiés du Cancéropôle Est :
Pr FLAMENT Stéphane, Dr GRILLIER-VUISSOZ Isabelle, Dr MAZERBOURG Sabine
Tous les auteurs :
Chbicheb S, Yao X, Rodeau JL, Salamone S, Boisbrun M, Thiel G, Spohn D, Grillier-Vuissoz I, Chapleur Y, Flament S, Mazerbourg S
Lien Pubmed
Résumé
Our aim was to get new information about the Peroxisome Proliferator Activated Receptor gamma (PPARgamma)-independent pathway involved in the antiproliferative action of PPARgamma ligands in breast cancer cells. We investigated the effects of Troglitazone (TGZ), Ciglitazone (CGZ), Rosiglitazone (RGZ) and, 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ(2)) on the hormone-dependent breast cancer cell line MCF7. The early transcription factor EGR1 (Early Growth Response gene 1) mRNA and protein levels peaked after 3h of incubation with 25muM TGZ, CGZ or 15d-PGJ(2) and then gradually decreased. RGZ, the most potent activator of PPARgamma, did not show this effect. The PPARgamma antagonist GW 9662 did not block EGR1 mRNA induction which also still occurred in case of PPARgamma silencing as well as in case of treatment with the PPARgamma-inactive compound Delta2-TGZ. EGR1 mRNA induction required ERK1/2 phosphorylation which was not blocked by EGF Receptor (EGFR) inhibition. The ERK1/2 pathway was also involved in Delta2-TGZ-induced EGR1 mRNA expression in the hormone-independent breast cancer cell line MDA-MB-231. Using the fluorescent dye Fura2, we showed in MCF7 that TGZ or Delta2-TGZ induced an immediate increase in cytosolic calcium which was required for ERK1/2 phosphorylation and EGR1 mRNA induction as demonstrated by calcium chelation experiments. Furthermore, in MCF7 transfected with siRNA targeting EGR1, Delta2-TGZ inhibited less efficiently cell proliferation.
Référence
Biochem Pharmacol. 2011 May 1;81(9):1087-97