%0 Journal Article
%T PPARs Signaling and Cancer in the Gastrointestinal System
%A Valerio Pazienza
%A Manlio Vinciguerra
%A Gianluigi Mazzoccoli
%J PPAR Research
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/560846
%X Nowadays, the study of the peroxisome proliferators activated receptors (PPARs) as potential targets for cancer prevention and therapy has gained a strong interest. From a biological point of view, the overall responsibility of PPARs in cancer development and progression is still controversial since several studies report both antiproliferative and tumor-promoting actions for these signaling molecules in human cancer cells and animal models. In this paper, we discuss PPARs functions in the context of different types of gastrointestinal cancer. 1. Introduction Since the discovery of the peroxisome proliferators activated receptors (PPARs) [1] in Xenopus frogs as receptors that induce the proliferation of peroxisomes in cells [2], three main forms transcribed from three different genes have been indentified: PPAR¦Á, PPAR¦Â/¦Ä, and PPAR¦Ã. Despite the little divergence of homology observed, each isoform possesses distinct biological activities and is expressed in different tissues [3]. PPAR¦Á is mainly expressed in the liver, the kidney, and the heart and is primarily involved in lipid metabolism. PPAR¦Ã is a master regulator of adipogenesis and fat storage: it regulates adipocyte differentiation and insulin sensitivity in adipose tissue. PPAR¦Â/¦Ä is found in a broad range of tissues but markedly expressed in brain, adipose tissue, and skin and its function awaits further exploration. PPARs are key mediators of energy homeostasis, lipid, and glucose metabolism although they have also been associated with other biological processes including development, differentiation, inflammation, atherosclerosis, wound healing, and tumor formation. All PPARs heterodimerize with the retinoid X receptor (RXR) to bind successively to specific DNA regions of target genes named PPREs (peroxisome proliferator hormone response elements). Like PPARs, RXR exists as three distinct isoforms: RXR¦Á, ¦Â, and ¦Ã, all of which are activated by the endogenous agonist 9-cis retinoic acid [4]. Contrasting observations confer to PPARs a double-edge sword nature in cancerogenesis, considering that either tumor suppressing or stimulating effects have been evidenced for these nuclear receptors [5]. PPARs function is modified by the specific shape of their ligand-binding domain induced by ligand binding and by a number of coactivator and corepressor proteins, the presence of which can stimulate or inhibit receptor function, respectively [6]. Endogenous ligands for the PPARs include free fatty acids and eicosanoids. PPAR isoform-specific agonists, specifically fibrates for PPAR¦Á and thiazolidinediones
%U http://www.hindawi.com/journals/ppar/2012/560846/