The nuclear eicosanoid receptor, PPARγ, is aberrantly expressed in colonic cancers

• Published in: Carcinogenesis (New York) Vol. 19; no. 1; pp. 49 - 53
• Main Authors: DUBOIS, R. N, GUPTA, R, BROCKMAN, J, REDDY, B. S, KRAKOW, S. L, LAZAR, M. A
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 1998
• Subjects: Biological and medical sciences; Gastroenterology. Liver. Pancreas. Abdomen; Medical sciences; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumors; Prostaglandin-endoperoxide synthase; Nuclear receptor; Rectal disease; Rat; Isozyme; Carcinogenesis; Eicosanoid; Intestinal disease; Colon; Tumor cell; Human; Enzyme; Rodentia; Malignant tumor; Gene expression; In vitro; Colonic disease; In vivo; Vertebrata; Mammalia; Cell line; Animal; Rectum; Digestive diseases; Oxidoreductases; Hormonal receptor
• ISSN: 0143-3334; 1460-2180
• DOI: 10.1093/carcin/19.1.49

Continuous use of nonsteroidal anti-inflammatory drugs (NSAIDs) lowers the relative risk of colorectal cancer in humans and decreases tumor yield in rodents treated with carcinogens. One well documented target for NSAIDs is prostaglandin endoperoxide synthase (cyclooxygenase) and two isoforms of this enzyme have been identified, cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). COX enzymes produce eicosanoid products, some of which have recently been shown to activate transcription mediated by the nuclear hormone receptor peroxisome proliferator activated receptor gamma (PPAR gamma ), whose expression is largely restricted to adipose tissue. The present study was undertaken to determine if PPAR gamma was expressed in colonic tumors. PPAR gamma messenger RNA (mRNA) and protein levels were assayed in colonic tumors and normal adjacent mucosa, as well as in a variety of human colon cancer cell lines. There was a marked increase in PPAR gamma RNA levels in four out of four of the colonic tumors compared to paired normal mucosa, where little expression of PPAR gamma was detected. Western blotting analysis showed that PPAR gamma protein was expressed in four out of five colonic tumor samples. PPAR gamma was also expressed in a subset of polyps, and in certain human colon cancer cell lines as well. Additionally, we were able to demonstrate that an eicosanoid, 15 deoxy- Delta 12,14 PGJ sub(2), transactivated transcription of a PPRE-driven promoter in CaCo-2 cells. Thus, we have shown that PPAR gamma gene and protein expression is elevated in rodent colon tumors, in selected human colon cancer cell lines and that the PPAR gamma receptor is functional in CaCo-2 cells. Since PPAR gamma is a ligand-modulated transcription factor, it may provide a novel target for chemopreventive strategies for colorectal cancer.