Relationship between peroxisome proliferator-activated receptor-γ expression and differentiation of human esophageal squamous cell carcinoma

Peroxisome proliferator-activated receptor-gamma (PPAR-γ), a member of the nuclear hormone receptor superfamily, is involved in suppressing the growth of several tumors. We showed that PPAR-γ is expressed in Barrett's adenocarcinoma cell lines and inhibited the growth of these lines through the induction of G1 cell cycle arrest and apoptosis. We examined PPAR-γ expression in human esophageal squamous cell carcinoma (SCC) in vitro and in vivo and investigated whether PPAR-γ ligands affect the proliferation and apoptosis of human SCC cell lines. Biopsy specimens (n=46) obtained from human SCC of the esophagus were stained using a monoclonal antibody against human PPAR-γ. We assessed the effects of PPAR-γ ligands on the growth of SCC cells by adding 15-deoxy prostaglandin J2 (15d-PGJ2), or troglitazone to six human esophageal SCC cell lines (TE-1, TE-2, TE-3, TE-5, TE-8, and TE-9). Immunohistochemical staining showed that 34 of 46 (73.9%) SCC of the esophagus expressed PPAR-γ. All SCC cell lines expressed PPAR-γ mRNA and protein, especially when poorly differentiated (TE-2, TE-5, and TE-9). The PPAR-γ ligands significantly and dose-dependently inhibited the proliferation of SCC lines, except for well-differentiated TE-1 and TE-3. Apoptosis was induced by 15d-PGJ2 (10 µM) in all tested SCC lines except TE-1, whereas troglitazone (50 µM) was marginally effective in only the TE-2 and TE-3 cell lines. The present findings suggest that PPAR-γ could be a therapeutic target for treating squamous cell carcinoma of the esophagus, possibly through the induction of apoptosis.