| Theme |
Molecular pathology of colorectal cancer for clinicians |
| Title |
PPAR gamma and colorectal cancers |
| Author |
Shinji Kitamura |
Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University |
| Author |
Yoshiji Miyazaki |
Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University |
| Author |
Miyuki Toyota |
Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University |
| Author |
Yasuhisa Shinomura |
Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University |
| [ Summary ] |
Peroxisome proliferator-activated receptor gamma (PPAR gamma) is a ligand-dependent nuclear receptor that has been implicated in the modulation of some aspects of development and homeostasis, including adipocyte differentiation and glucose metabolism. Several polyunsaturated fatty acids, the thiazolidindione class of antidiabetic drugs and the nuclear prostanoid 15-deoxy delta12,14-prostaglandin J2 have been identified as ligands for PPAR delta. Although adipose tissue is a principle site of PPAR gamma expression, this receptor is also expressed at significant levels in several other tissues, including normal and neoplastic tissues of the large intestine. There is a controversy concerning the effects of PPAR gamma on colonic tumorigenesis. Some reports indicate that PPAR gamma ligands induce growth arrest and differentiation of colorectal cancer cells. In contrast, others describe PPAR gamma activators as promoting the development of colon tumors in Min mice, which lack a single copy of adenomatous polyposis coli (APC) tumor suppressor gene. This discrepancy is not yet understood. A recent study reports that PPAR delta is identified as a target of APC gene and that chemopreventive nonsteroidal anti-inflammatory drugs inhibit tumorigenesis through inhibition of PPAR delta. PPARs are now attracting attention for use in therapeutic intervention in disorders such as obesity, diabetes, atherosclerosis, chronic inflammatory diseases, and tumorigenesis. |