The role of peroxisome proliferator-activated receptor β/δ in colorectal cancer

• Main Author: Tan, Eddie Han Pin
• Other Authors: Tan Nguan Soon, Andrew
• Format: Theses and Dissertations
• Language: English
• Published: 2018
• Subjects: DRNTU::Science::Biological sciences::Molecular biology
• Online Access: http://hdl.handle.net/10356/74230
• Institution: Nanyang Technological University

Peroxisome proliferator–activated receptor β/δ (PPAR β/δ) is overexpressed in human colon cancer, but its contribution to colonic tumorigenesis is controversial. We generated a mouse model in which PPARβ/δ was genetically disrupted in the fibroblasts (FSPCre-Pparb/d-/-). FSPCre-Pparb/d-/- mice were less susceptible to DSS-induced colitis, developed fewer intestinal polyps and survived longer when compared with Pparb/dfl/fl mice. Comparative gene expression analysis of epithelial and mucosal layers revealed enhanced NRF2-mediated stress responses in intestinal epithelium owing to the deletion of fibroblast PPARβ/δ. The pre-treatment of FSPCre-Pparb/d−/− and Pparb/dfl/fl with antioxidant N-acetyl-cysteine prior DSS-induced tumorigenesis resulted in lower tumor load.