Activation of peroxisome proliferator-activated receptor (PPAR)-γ induces terminal differentiation and growth inhibition associated with G1 cell cycle arrest in some cancer cells. The multifunctional molecule β-catenin performs important roles in intercellular adhesion and signal transduction. However, no report has focused on actions of PPAR-γ in regulating the E-cadherin/β-catenin system. We examined whether thiazolidinedione (TZD), a potent PPAR-γ ligand, could modulate the E-cadherin/β-catenin system in a human pancreatic cancer cell line, BxPC-3, that has been found to express PPAR-γ. According to Western blotting, TZD markedly increased differentiation markers including E-cadherin and carcinoembryonic antigen, while β-catenin did not change significantly. In untreated cells, fluorescence immunostaining demonstrated β-catenin predominantly in the cytoplasm and/or nucleus; in TZD-treated cells, β-catenin localization had dramatically shifted to the plasma membrane, in association with increased E-cadherin at this site. Thus, a PPAR-γ ligand appears to participate not only in induction of differentiation in pancreatic cancer cells, but also in the regulation of the E-cadherin/β-catenin system. Such ligands may prove clinically useful as cytostatic anticancer agents.

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