Role of PPARγ in the growth, differentiation and apoptosis of gastrointestinal epithelial cells.

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Several colonic and gastric cancer cell lines express peroxisome proliferator activated receptor γ (PPARγ), a member of the nuclear receptor superfamily. The purpose of the present study was to clarify the role of PPARγ in the growth and differentiation of gastrointestinal epithelial cells and to evaluate the possibility that ligands for PPARγ can be effective for the treatment of gastrointestinal carcinoma.1. Activation of PPARγ inhibits the growth of HT-29 colonic cancer cells and induces the differentiation markers.2. Ligand activation of PPARγ reduces the expression of c-Met tyrosine kinase at the transcriptional level. This may be one mechanism, by which activation of PPARγ inhibits the growth of MKN-45 gastric cancer cells.3. We created a cell line, IECrasPR82 that expresses both oncogenic ras and PPARγ by DNA transfection. Activation of PPARγ inhibits the growth of this cell line.4. Ligands for PPARγ inhibit the expression of heparin-binding EGF-like growth factor (HB-EGF), amphiregulin and cyclin D1 through the suppression of AP-1 and Ets.5. Thus PPARγ ligands may be candidates for a novel approach to the treatment of gastric and colorectal cancers.