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Abstract
Peroxisome proliferator-activated receptors gamma (PPARγ) is a transcriptional factor belonging to the ligand-activated nuclear receptor superfamily. PPARγ is highly expressed in adipose tissue and has a dominant regulatory role in adipocyte differentiation. In humans, PPARγ is expressed in multiple tissues such as the breast, colon, lung, ovary, and placenta. In addition to adipogenic and anti-inflammatory effects, PPARγ activation has been shown to be anti-proliferative by virtue of its differentiation-promoting effect, suggesting that activation of PPARγ may be useful in slowing or arresting the proliferation of de-differentiated tumor cells. A number of PPARγ ligands, such as natural prostaglandins and synthetic anti-diabetic thiazolidinediones (TZDs), have been identified. The discovery of PPARγ agonists has enabled the elucidation of the mechanisms involved in the multiple effects of PPARγ on the inhibition of tumor cell growth. The importance of this transcription factor in physiology and pathophysiology has stimulated much research in this field. This review describes structural features of PPARγ, mechanisms of PPARγ gene transcription, and recent developments in the discovery of its biological functions on growth inhibition of lung tumors. Prospects for future research leading to new therapies for lung cancer are also discussed.
Key words :
| Abbreviations | ||
| α5 | = | α5 subunit of the α5β1 fibronectin integrin receptor |
| 9-HODE | = | 9-hydroxyoctadecadienoic acid |
| 13-HODE | = | 13-hydroxyoctadecadienoic acid |
| 5-HETE | = | 15-hydroxyeicosatetraenoic acid |
| AF-1 | = | ligand-independent activation function 1 |
| AF-2 | = | ligand-dependent activation function 2 |
| DBD | = | DNA binding domain |
| 15d-PGJ2 | = | 15-deoxy-delta12-14-prostaglandin J2 |
| DR | = | direct repeat |
| EGF | = | epidermal growth factor |
| ELR+CXC chemokines | = | the CXC chemokine family consisting of a three-amino-acid motif of glutamic acid-leucine-arginine (ELR motif) residues |
| EP2 | = | PGE2 receptor |
| ERK | = | extracellular signal-regulated kinase |
| GADD | = | growth arrest and DNA-damage inducible |
| JNK | = | c-Jun N-terminal kinase |
| LBD | = | ligand-binding domain |
| MAPK | = | mitogen-activated protein kinase |
| Δp∼ | = | mitochondrial membane potential |
| MKK1 | = | ERK MAPK-kinase |
| MMP-2 | = | matrix metalloproteinase-2 |
| NSAIDs | = | nonsteroidal anti-inflammatory drugs |
| NSCLC | = | non-small cell lung cancer |
| PBP | = | PPAR binding protein |
| PDGF | = | platelet-derived growth factor |
| PG | = | prostaglandin |
| PGE2 | = | prostaglandin E2 |
| PGJ2 | = | prostaglandin J2 |
| PPAR | = | peroxisome proliferator-activated receptor |
| PPARγ | = | peroxisome proliferator-activated receptor gamma |
| PPRE | = | peroxisome proliferator responsive element |
| RARβ | = | retinoic acid receptor beta |
| RXR | = | retinoid X receptor |
| SCLC | = | small cell lung cancer |
| SRC | = | steroid receptor co-activator |
| TGF | = | tumor growth factor |
| TGZ | = | troglitazone |
| TZD | = | synthetic anti-diabetic thiazolidinedione |
| U0126 | = | specific inhibitor of ERK |
| Abbreviations | ||
| α5 | = | α5 subunit of the α5β1 fibronectin integrin receptor |
| 9-HODE | = | 9-hydroxyoctadecadienoic acid |
| 13-HODE | = | 13-hydroxyoctadecadienoic acid |
| 5-HETE | = | 15-hydroxyeicosatetraenoic acid |
| AF-1 | = | ligand-independent activation function 1 |
| AF-2 | = | ligand-dependent activation function 2 |
| DBD | = | DNA binding domain |
| 15d-PGJ2 | = | 15-deoxy-delta12-14-prostaglandin J2 |
| DR | = | direct repeat |
| EGF | = | epidermal growth factor |
| ELR+CXC chemokines | = | the CXC chemokine family consisting of a three-amino-acid motif of glutamic acid-leucine-arginine (ELR motif) residues |
| EP2 | = | PGE2 receptor |
| ERK | = | extracellular signal-regulated kinase |
| GADD | = | growth arrest and DNA-damage inducible |
| JNK | = | c-Jun N-terminal kinase |
| LBD | = | ligand-binding domain |
| MAPK | = | mitogen-activated protein kinase |
| Δp∼ | = | mitochondrial membane potential |
| MKK1 | = | ERK MAPK-kinase |
| MMP-2 | = | matrix metalloproteinase-2 |
| NSAIDs | = | nonsteroidal anti-inflammatory drugs |
| NSCLC | = | non-small cell lung cancer |
| PBP | = | PPAR binding protein |
| PDGF | = | platelet-derived growth factor |
| PG | = | prostaglandin |
| PGE2 | = | prostaglandin E2 |
| PGJ2 | = | prostaglandin J2 |
| PPAR | = | peroxisome proliferator-activated receptor |
| PPARγ | = | peroxisome proliferator-activated receptor gamma |
| PPRE | = | peroxisome proliferator responsive element |
| RARβ | = | retinoic acid receptor beta |
| RXR | = | retinoid X receptor |
| SCLC | = | small cell lung cancer |
| SRC | = | steroid receptor co-activator |
| TGF | = | tumor growth factor |
| TGZ | = | troglitazone |
| TZD | = | synthetic anti-diabetic thiazolidinedione |
| U0126 | = | specific inhibitor of ERK |