Induction of Metastatic Gastric Cancer by Peroxisome Proliferator-Activated Receptorδ Activation

Figure 4

Immunohistochemical analysis of forestomach after GW501516 treatment and gastric tumors. IHC detection of PPARδ, pS473Akt, pT308 Akt, PDK1, β-catenin, and S100a9. Magnification: untreated and GW501516 treated, 400x; tumor, PPARδ, PDK1, and β-catenin, 200x; pT308Akt, pS473Akt, S100a9, and 400x. Inset, 2x original magnification. PPARδ shows diffuse reactivity in untreated gastric squamous epithelium, increased nuclear localization after GW501516 treatment, and strong nuclear expression in tumor and stromal cells (inset). pS473Akt and pT308Akt expressed weak diffuse reactivity in untreated gastric tissue, increased staining in basal cells and the submucosal cell layer after GW501516 treatment, and strong reactivity in tumor and stromal cells. PDK1 exhibited diffuse cytoplasmic localization throughout the untreated squamous epithelium and was unchanged after GW501516 treatment, whereas PDK1 was increased in tumors similarly to pS473Akt and pT308Akt. Nuclear β-catenin was present in basal cells of untreated squamous epithelium and was unchanged after GW501516 treatment, whereas tumors expressed increased β-catenin at cellular junctions (inset). S100a9 was undetectable in untreated tissue and was increased in blood vessels and squamous epithelium (inset), whereas tumors exhibited increased diffuse cytoplasmic staining.