The role of peroxisome proliferator-activated receptor β/δ in colorectal cancer
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...
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| Format: | Theses and Dissertations |
| Language: | English |
| Published: |
2018
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| Online Access: | http://hdl.handle.net/10356/74230 |
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| Institution: | Nanyang Technological University |
| Language: | English |
| Summary: | 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. |
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