Relationship between peroxisome proliferator-activated receptor-gamma expression and differentiation of human esophageal squamous cell carcinoma.
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.
Takashima
Takashi
T
Department of Gastroenterology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan. d98m011@ med.osaka-cu.ac.jp
Fujiwara
Yasuhiro
Y
Hamaguchi
Masaki
M
Sasaki
Eiji
E
Tominaga
Kazunari
K
Watanabe
Toshio
T
Oshitani
Nobuhide
N
Higuchi
Kazuhide
K
Arakawa
Tetsuo
T
D000911:Antibodies, Monoclonal / Q000737:chemistry; D017209:Apoptosis; D001471:Barrett Esophagus / Q000378:metabolism* / Q000473:pathology; D001706:Biopsy; D006690:Bisbenzimidazole / Q000494:pharmacology; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002839:Chromans / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology; D016193:G1 Phase; D006801:Humans; D007150:Immunohistochemistry; D008024:Ligands; D047495:PPAR gamma / Q000096:biosynthesis*; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000494:pharmacology; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D045162:Thiazolidinediones / Q000494:pharmacology; D013936:Thymidine / Q000737:chemistry; D000077288:Troglitazone
C477819:15-deoxyprostaglandin J2; D000911:Antibodies, Monoclonal; D002839:Chromans; D008024:Ligands; D047495:PPAR gamma; D012333:RNA, Messenger; D045162:Thiazolidinediones; D012313:RNA; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D000077288:Troglitazone; D006690:Bisbenzimidazole; D015230:Prostaglandin D2; D013936:Thymidine