Details

Autor(en) / Beteiligte

• Al-Taie, Oliver H
• Graf, Tilmann
• Illert, Bertram
• Katzenberger, Tiemo
• Mörk, Hubert
• Kraus, Michael R
• Barthelmes, Hans U
• Scheurlen, Michael
• Seufert, Jochen

Titel

Differential effects of PPARγ activation by the oral antidiabetic agent pioglitazone in Barrett's carcinoma in vitro and in vivo

Ist Teil von

• Journal of gastroenterology, 2009-09, Vol.44 (9), p.919-929

Ort / Verlag

Japan: Japan : Springer Japan

Erscheinungsjahr

2009

Link zum Volltext

Quelle

SpringerLink

Beschreibungen/Notizen

• Background and purpose The nuclear hormone receptor peroxisome proliferator-activated receptor gamma (PPARγ) is a key transcription factor regulating genes involved in adipogenesis, glucose homeostasis and cell differentiation. Moreover, PPARγ has been demonstrated to control proliferation and apoptosis in various cancer cells. We investigated the biological effects of PPARγ activation by the oral antidiabetic agent pioglitazone in Barrett's adenocarcinoma cells in vitro and in vivo. Results PPARγ 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. PPARγ activation by pioglitazone in OE33 cells in vitro led to reduced cell growth by induction of apoptosis. Effects of systemic PPARγ 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. Conclusion These results indicate that PPARγ is involved in the molecular pathogenesis of Barrett's adenocarcinoma formation and growth. However, activation of PPARγ 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 PPARγ action in vivo.