| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA
2 Atlanta Veterans Affairs Medical Center, Atlanta, GA, USA
3 Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA; Atlanta Veterans Affairs Medical Center, Atlanta, GA, USA
* To whom correspondence should be addressed. E-mail: shan2{at}emory.edu.
Lung carcinoma often occurs in patients with chronic lung disease such as tobacco-related emphysema and asbestos-related pulmonary fibrosis. These diseases are characterized by dramatic alterations in the content and composition of the lung extracellular matrix, and we believe that this altered matrix has the ability to promote lung carcinoma cell growth. One extracellular matrix molecule shown to be altered in these lung diseases is fibronectin (Fn). We previously reported increased growth and survival of non-small-cell lung carcinoma (NSCLC) cells exposed to Fn. Thus, Fn may serve as a mitogen/survival factor for NSCLC and therefore represents a novel target for anti-cancer strategies. To this end, we studied the effects of the PPAR
ligands, 15d-PGJ2, rosiglitazone (BRL49653) and troglizatone, on Fn expression in NSCLC cells and found that they were able to inhibit Fn gene expression. Inhibition of Fn expression by BRL49653 and troglitazone, but not by 15d-PGJ2, was prevented by the specific PPAR antagonist GW9662, and by PPAR siRNA. Working with Fn deletion and mutated promoter constructs, we found that the region between -170 to -50 base pairs downstream from the transcriptional start site of the promoter was involved in PPAR ligand inhibition. PPAR ligands also diminished the phosphorylation of cyclic adenosine monophosphate response element binding protein (CREB), diminished Sp1 nuclear protein expression, and prevented the binding of these transcription factors to CRE and Sp1 sites, respectively, within the Fn promoter. In summary, our results demonstrate that PPAR ligands inhibit Fn gene expression in NSCLC cells through PPAR-dependent and -independent pathways that affect both CREB and Sp1.
This article has been cited by other articles:
|
|
 |
|
  D. Gunnarsson, P. Leffler, E. Ekwurtzel, G. Martinsson, K. Liu, and G. Selstam Mono-(2-ethylhexyl) phthalate stimulates basal steroidogenesis by a cAMP-independent mechanism in mouse gonadal cells of both sexes Reproduction, May 1, 2008; 135(5): 693 - 703. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V Costa, D Foti, F Paonessa, E Chiefari, L Palaia, G Brunetti, E Gulletta, A Fusco, and A Brunetti The insulin receptor: a new anticancer target for peroxisome proliferator-activated receptor-{gamma} (PPAR{gamma}) and thiazolidinedione-PPAR{gamma} agonists Endocr. Relat. Cancer, March 1, 2008; 15(1): 325 - 335. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Peraza, A. D. Burdick, H. E. Marin, F. J. Gonzalez, and J. M. Peters The Toxicology of Ligands for Peroxisome Proliferator-Activated Receptors (PPAR) Toxicol. Sci., April 1, 2006; 90(2): 269 - 295. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
