[The role of peroxisome proliferator-activated receptors (PPAR) in carcinogenesis].
Peroxisome proliferators-activated receptors are members of the nuclear hormone receptor superfamily of ligand-activated transcription factors. The PPAR subfamily consists of three members: PPAR-alpha, PPAR-sigma (NUC-1 or beta) and PPAR-gamma. PPARs regulate gene expression by binding, as heterodimers with retinoid X receptors (RXR), to specific response elements (PPREs) in the promoter regions of target genes. The prostaglandin 12 especially, all arachidonic acid metabolites and polyunsaturated fatty acids are naturally occuring PPAR ligands. Synthetic PPAR ligands are thiazolidinediones (TZDs--rosiglitazone, pioglitazone, troglitazone). Activation of nuclear hormone receptors has been identified as an approach to induce differentiation and inhibit proliferation of cancer lines. The anti-proliferative, pro-differentiation effects of PPAR activators (TZDs) suggest that these compounds might be useful in slowing the proliferation of un-differentiated tumour cells. TZDs inhibit proliferation of human breast, prostate and colon cancers, both in vitro and in tumours derived from these cells implanted into rodents. Furthermore, recent studies show that PPAR-gamma ligands are potent inhibitors of angiogenesis, a process essential for solid-tumour growth and metastasis. In conclusion, the evidence to date suggests that activation of PPAR should suppress tumour growth and development. This represents an exciting novel therapeutic application of TZDs. In present paper, structural features of PPARs, their gene transcription mechanisms and recent developments in the discovery of their biological functions are reviewed.
Knapp
Paweł
P
Klinika Ginekologii, Akademia Medyczna w Białymstoku. knapp@pb.bialystok.pl
Jarzabek
Katarzyna
K
Błachnio
Agnieszka
A
Zbroch
Tomasz
T
D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism*; D047493:PPAR alpha / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D048068:PPAR-beta / Q000378:metabolism; D047492:Peroxisome Proliferator-Activated Receptors / Q000235:genetics / Q000378:metabolism*; D020675:Peroxisomes / Q000235:genetics / Q000378:metabolism*
D047493:PPAR alpha; D047495:PPAR gamma; D048068:PPAR-beta; D047492:Peroxisome Proliferator-Activated Receptors