title: Differential effects of PPARgamma activation by the oral antidiabetic agent pioglitazone in Barrett's carcinoma in vitro and in vivo.
abstract: OBJECTIVE
  The nuclear hormone receptor peroxisome proliferator-activated receptor gamma (PPARgamma) is a key transcription factor regulating genes involved in adipogenesis, glucose homeostasis and cell differentiation. Moreover, PPARgamma has been demonstrated to control proliferation and apoptosis in various cancer cells. We investigated the biological effects of PPARgamma activation by the oral antidiabetic agent pioglitazone in Barrett's adenocarcinoma cells in vitro and in vivo.
  
  
  RESULTS
  PPARgamma mRNA and protein were overexpressed in endoscopic biopsies of Barrett's epithelium and the human Barrett's adenocarcinoma cancer cell line OE33 as compared to normal esophagus and stomach and the esophageal squamous epithelium cancer cell line Kyse-180. PPARgamma activation by pioglitazone in OE33 cells in vitro led to reduced cell growth by induction of apoptosis. Effects of systemic PPARgamma activation by the thiazolidinedione pioglitazone on tumor cell proliferation and apoptosis were then assessed in vivo in nude mice bearing transplantable Barrett's adenocarcinomas derived from OE33 cells. Unexpectedly, enhanced growth of OE33 derived transplantable adenocarcinomas was observed in Balb/c nu/nu mice upon systemic pioglitazone treatment due to increased cell proliferation.
  
  
  CONCLUSIONS
  These results indicate that PPARgamma is involved in the molecular pathogenesis of Barrett's adenocarcinoma formation and growth. However, activation of PPARgamma exerts differential effects on growth of Barrett's adenocarcinoma cells in vitro and in vivo emphasizing the importance of additional cell context specific factors and systemic metabolic status for the modulation of PPARgamma action in vivo.
authors.affiliation: Medizinische Klinik II, Klinikum Aschaffenburg, Am Hasenkopf 1, 63739, Aschaffenburg, Germany. oliver.altaie@klinikum-aschaffenburg.de
authors.forename: Oliver H
authors.initials: OH
authors.lastname: Al-Taie
authors.forename: Tilmann
authors.initials: T
authors.lastname: Graf
authors.forename: Bertram
authors.initials: B
authors.lastname: Illert
authors.forename: Tiemo
authors.initials: T
authors.lastname: Katzenberger
authors.forename: Hubert
authors.initials: H
authors.lastname: Mörk
authors.forename: Michael R
authors.initials: MR
authors.lastname: Kraus
authors.forename: Hans U
authors.initials: HU
authors.lastname: Barthelmes
authors.forename: Michael
authors.initials: M
authors.lastname: Scheurlen
authors.forename: Jochen
authors.initials: J
authors.lastname: Seufert
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001471:Barrett Esophagus / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D047495:PPAR gamma / Q000187:drug effects* / Q000378:metabolism; D000077205:Pioglitazone; D012333:RNA, Messenger; D045162:Thiazolidinediones / Q000494:pharmacology*
chemical_list: D007004:Hypoglycemic Agents; D047495:PPAR gamma; D012333:RNA, Messenger; D045162:Thiazolidinediones; D000077205:Pioglitazone