© The Author 2007. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Mechanistic Evaluation of PPAR
-Mediated Hepatocarcinogenesis: Are We There Yet?
Department of Veterinary and Biomedical Sciences and Center for Molecular Toxicology and Carcinogenesis, 312 Life Sciences Building, The Pennsylvania State University, University Park, Pennsylvania 16802
1 For correspondence via fax: (814) 863-1696. E-mail: jmp21@psu.edu.
Received September 14, 2007; accepted September 26, 2007
Key Words: peroxisome proliferators; peroxisome proliferator-activated receptor-
; liver cancer; humanized mouse models.
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The fibrate class of hypolipidemic drugs have been used for many years as therapeutic agents to reduce serum triglycerides, increase serum high density lipoprotein cholesterol, and in doing so, improve the health of individuals with dyslipidemias. Long before the actual mechanism of action was delineated, it was postulated that these drugs functioned by activating a nuclear receptor. Indeed, the identification and cloning of the peroxisome proliferator–activated receptor- (PPAR) (Issemann and Green, 1990
) led to a plethora of research that definitively confirmed that PPAR was the central mediator for the hypolipidemic effects of fibrates. But the story actually became significantly more complicated over the years because it turned out that there were many other chemicals, collectively termed "peroxisome proliferators" that activated this receptor. More importantly, the seminal