Function of PPAR-γ and its ligands in lung cancer

Peroxisome Proliferator-activated receptors gamma (PPAR gamma) is a transcriptional factor belonging to the ligand-activated nuclear receptor superfamily. PPAR gamma is highly expressed in adipose tissue and has a dominant regulatory role in adipocyte differentiation. In humans, PPAR gamma is expressed in multiple tissues such as the breast, colon, lung, ovary, and placenta. In addition to adipogenic and anti-inflammatory effects, PPAR gamma activation has been shown to be anti-proliferative by, virtue of its differentiation-promoting effect, suggesting that activation of PPAR gamma may be useful in slowing or arresting the proliferation of de-differentiated tumor cells. A number of PPAR gamma ligands, such as natural prostaglandins and synthetic anti-diabetic thiazolidinediones (TZDs), have been identified. The discovery of PPAR gamma agonists has enabled the elucidation of the mechanisms involved in the multiple effects of PPAR gamma an 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 fratures of PPAR gamma, mechanisms of PPAR gamma 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.