alexa Peroxisome proliferator-activated receptor-alpha and liver cancer: where do we stand?


Journal of Carcinogenesis & Mutagenesis

Author(s): Peters JM, Cheung C, Gonzalez FJ

Abstract Share this page

Abstract The peroxisome proliferator-activated receptor-alpha (PPARalpha), first identified in 1990 as a member of the nuclear receptor superfamily, has a central role in the regulation of numerous target genes encoding proteins that modulate fatty acid transport and catabolism. PPARalpha is the molecular target for the widely prescribed lipid-lowering fibrate drugs and the diverse class of chemicals collectively referred to as peroxisome proliferators. The lipid-lowering function of PPARalpha occurs across a number of mammalian species, thus demonstrating the essential role of this nuclear receptor in lipid homeostasis. In contrast, prolonged administration of PPARalpha agonists causes hepatocarcinogenesis, specifically in rats and mice, indicating that PPARalpha also mediates this effect. There is no strong evidence that the low-affinity fibrate ligands are associated with cancer in humans, but it still remains a possibility that chronic activation with high-affinity ligands could be carcinogenic in humans. It is now established that the species difference between rodents and humans in response to peroxisome proliferators is due in part to PPARalpha. The cascade of molecular events leading to liver cancer in rodents involves hepatocyte proliferation and oxidative stress, but the PPARalpha target genes that mediate this response are unknown. This review focuses on the current understanding of the role of PPARalpha in hepatocarcinogenesis and identifies future research directions that should be taken to delineate the mechanisms underlying PPARalpha agonist-induced hepatocarcinogenesis. This article was published in J Mol Med (Berl) and referenced in Journal of Carcinogenesis & Mutagenesis

Relevant Expert PPTs

Relevant Speaker PPTs

Peer Reviewed Journals
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version