234
Views
22
CrossRef citations to date
0
Altmetric
Research Article

Function of Pparγ and Its Ligands in Lung Cancer

, , &
Pages 183-202 | Published online: 10 Oct 2008
 

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.

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

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.