title: Involvement of PPAR gamma and E-cadherin/beta-catenin pathway in the antiproliferative effect of conjugated linoleic acid in MCF-7 cells.
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, PPAR gamma is involved in growth inhibition of transformed cells. Ligands of PPAR gamma are considered as potential anticancer drugs, so CLA was tested for its ability to induce PPAR gamma expression in MCF-7 breast cancer cells. The effects of CLA and of a specific synthetic PPAR gamma 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 PPAR gamma to levels up to control and caused PPAR gamma translocation into the nucleus. Furthermore, the overexpression of PPAR gamma 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 beta-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 beta-catenin and E-cadherin and the antagonist reverted only the effect on beta-catenin. These studies indicate that CLA regulates PPAR gamma expression by selectively acting as an agonist and may influence cell-cell adhesion and invasiveness of MCF-7 cells.
authors.affiliation: Department of Experimental Medicine and Oncology, University of Torino, Torino, Italy. claudia.bocca@unito.it
authors.forename: Claudia
authors.initials: C
authors.lastname: Bocca
authors.forename: Francesca
authors.initials: F
authors.lastname: Bozzo
authors.forename: Simona
authors.initials: S
authors.lastname: Francica
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Colombatto
authors.forename: Antonella
authors.initials: A
authors.lastname: Miglietta
mesh_terms: D000199:Actins / Q000378:metabolism; D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D007424:Intracellular Fluid / Q000378:metabolism; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008856:Microscopy, Fluorescence; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D014404:Tubulin / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D000199:Actins; D015820:Cadherins; D044243:Linoleic Acids, Conjugated; D047495:PPAR gamma; D014404:Tubulin; D051176:beta Catenin; D048049:Extracellular Signal-Regulated MAP Kinases