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

Oncol Rep. 2005 Apr;13(4):601-6.


Peroxisome proliferator-activated receptor-gamma (PPAR-gamma), a member of the nuclear hormone receptor superfamily, is involved in suppressing the growth of several tumors. We showed that PPAR-gamma 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-gamma expression in human esophageal squamous cell carcinoma (SCC) in vitro and in vivo and investigated whether PPAR-gamma 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-gamma. We assessed the effects of PPAR-gamma 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-gamma. All SCC cell lines expressed PPAR-gamma mRNA and protein, especially when poorly differentiated (TE-2, TE-5, and TE-9). The PPAR-gamma 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 microM) in all tested SCC lines except TE-1, whereas troglitazone (50 microM) was marginally effective in only the TE-2 and TE-3 cell lines. The present findings suggest that PPAR-gamma could be a therapeutic target for treating squamous cell carcinoma of the esophagus, possibly through the induction of apoptosis.

MeSH terms

  • Antibodies, Monoclonal / chemistry
  • Apoptosis
  • Barrett Esophagus / metabolism*
  • Barrett Esophagus / pathology
  • Biopsy
  • Bisbenzimidazole / pharmacology
  • Blotting, Western
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Caspase 3
  • Caspases / metabolism
  • Cell Differentiation
  • Cell Line, Tumor
  • Cell Proliferation
  • Chromans / pharmacology
  • Dose-Response Relationship, Drug
  • Esophageal Neoplasms / metabolism*
  • Esophageal Neoplasms / pathology
  • G1 Phase
  • Humans
  • Immunohistochemistry
  • Ligands
  • PPAR gamma / biosynthesis*
  • Prostaglandin D2 / analogs & derivatives
  • Prostaglandin D2 / pharmacology
  • RNA / metabolism
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Thiazolidinediones / pharmacology
  • Thymidine / chemistry
  • Troglitazone


  • 15-deoxyprostaglandin J2
  • Antibodies, Monoclonal
  • Chromans
  • Ligands
  • PPAR gamma
  • RNA, Messenger
  • Thiazolidinediones
  • RNA
  • CASP3 protein, human
  • Caspase 3
  • Caspases
  • Troglitazone
  • Bisbenzimidazole
  • Prostaglandin D2
  • Thymidine