Involvement of PPARγ and E-cadherin/β-catenin pathway in the antiproliferative effect of conjugated linoleic acid in MCF-7 cells

✍ Scribed by Claudia Bocca; Francesca Bozzo; Simona Francica; Sebastiano Colombatto; Antonella Miglietta

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: French
• Weight: 777 KB
• Volume: 121
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.22646

✦ Synopsis

Abstract

Conjugated linoleic acid (CLA) is a naturally occurring fatty acid, which has been shown to exert beneficial effects against breast carcinogenesis. It has been reported that CLA could modulate cellular proliferation and differentiation through the activation of peroxisome proliferator‐activated receptors (PPARs). Among different PPAR isotypes, PPARγ is involved in growth inhibition of transformed cells. Ligands of PPARγ are considered as potential anticancer drugs, so CLA was tested for its ability to induce PPARγ expression in MCF‐7 breast cancer cells. The effects of CLA and of a specific synthetic PPARγ antagonist were evaluated on cell growth as well as on parameters responsible for cell growth regulation. We demonstrated here that CLA stimulated the expression of PPARγ to levels up to control and caused PPARγ translocation into the nucleus. Furthermore, the overexpression of PPARγ positively correlates with the inhibition of cell proliferation and with the modulation of ERK signaling induced by CLA; in all cases the administration of the antagonist reverted CLA effects. The PPAR‐signaling pathway is connected with the β‐catenin/E‐cadherin pathway, thus we evaluated CLA effects on the expression and cellular distribution of these proteins, which are involved in cell adhesion and responsible for invasive behavior. The treatment with CLA determined the up‐regulation and the redistribution of β‐catenin and E‐cadherin and the antagonist reverted only the effect on β‐catenin. These studies indicate that CLA regulates PPARγ expression by selectively acting as an agonist and may influence cell–cell adhesion and invasiveness of MCF‐7 cells. © 2007 Wiley‐Liss, Inc.