![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Laboratory of Molecular Carcinogenesis (S.J.B., J.-S.K., S.M.M., T.E.E.) and Laboratory of Computational Biology and Risk Analysis (J.M.), National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina; and Laboratory of Environmental Carcinogenesis, Department of Pathobiology, College of Veterinary Medicine, University of Tennessee, Knoxville, Tennessee (S.J.B., S.-H.L.)
Abstract
Nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to have chemopreventive activity, but the mechanisms involved are not clearly understood. Although NSAIDs inhibit cyclooxygenase activity, they also increase the expression of a divergent member of the transforming growth factor-
superfamily, termed NSAID-activated gene 1 (NAG-1), a protein with an antitumorigenic and proapoptotic activity that could in part be linked to the chemoprevention activity of NSAIDs. NAG-1 is induced by some NSAIDs, but the mechanisms responsible are not clear. In this report, we have identified a cis-acting element responsive to NSAIDs located within the –73 to –51 region of the NAG-1 promoter. This region contains overlapping EGR-1 and Sp1 binding sites, and mutations in this region suggest that the transcription factors have an important role in NSAID-induced NAG-1 expression. EGR-1 was found to play a critical role in the induction of NAG-1 by sulindac sulfide and other NSAIDs. NSAIDs increase EGR-1 protein expression that occurs before the induction of NAG-1 expression, supporting the hypothesis that EGR-1 is necessary for NSAID-induced NAG-1 expression. Thus, NSAIDs induce the expression of EGR-1, a tumor suppressor gene, providing a novel mechanism to explain, in part, the antitumorigenic properties of some NSAIDs. NAG-1 seems to be an important downstream target protein of this transcription factor, EGR-1, and may mediate the chemopreventive activity of some NSAIDs.
Address correspondence to: Dr. Thomas E. Eling, Laboratory of Molecular Carcinogenesis, 111 TW Alexander Drive, Research Triangle Park, NC 27709. E-mail: Eling{at}niehs.nih.gov
This article has been cited by other articles:
|
|
 |
|
  C.-C. Wu, J.-C. Lin, S.-C. Yang, C.-W. Lin, J. J.W. Chen, J.-Y. Shih, T.-M. Hong, and P.-C. Yang Modulation of the expression of the invasion-suppressor CRMP-1 by cyclooxygenase-2 inhibition via reciprocal regulation of Sp1 and C/EBP{alpha} Mol. Cancer Ther., June 1, 2008; 7(6): 1365 - 1375. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M.-R. Pan, H.-C. Chang, L.-Y. Chuang, and W.-C. Hung The Nonsteroidal Anti-Inflammatory Drug NS398 Reactivates SPARC Expression via Promoter Demethylation to Attenuate Invasiveness of Lung Cancer Cells Experimental Biology and Medicine, April 1, 2008; 233(4): 456 - 462. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Papineni, S. Chintharlapalli, and S. Safe Methyl 2-Cyano-3,11-dioxo-18{beta}-olean-1,12-dien-30-oate Is a Peroxisome Proliferator-Activated Receptor-{gamma} Agonist That Induces Receptor-Independent Apoptosis in LNCaP Prostate Cancer Cells Mol. Pharmacol., February 1, 2008; 73(2): 553 - 565. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-L. Chen, P.-C. Lin, S.-P. Chen, C.-C. Lin, N.-M. Tsai, Y.-L. Cheng, W.-L. Chang, S.-Z. Lin, and H.-J. Harn Activation of Nonsteroidal Anti-Inflammatory Drug-Activated Gene-1 via Extracellular Signal-Regulated Kinase 1/2 Mitogen-Activated Protein Kinase Revealed a Isochaihulactone-Triggered Apoptotic Pathway in Human Lung Cancer A549 Cells J. Pharmacol. Exp. Ther., November 1, 2007; 323(2): 746 - 756. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T Ichikawa, K Horie-Inoue, K Ikeda, B Blumberg, and S Inoue Vitamin K2 induces phosphorylation of protein kinase A and expression of novel target genes in osteoblastic cells J. Mol. Endocrinol., October 1, 2007; 39(4): 239 - 247. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Zhou, Y. Zhong, Y. Wang, X. Zhang, D. L. Batista, R. Gejman, P. J. Ansell, J. Zhao, C. Weng, and A. Klibanski Activation of p53 by MEG3 Non-coding RNA J. Biol. Chem., August 24, 2007; 282(34): 24731 - 24742. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Soto-Cerrato, F. Vinals, J. R. Lambert, J. A. Kelly, and R. Perez-Tomas Prodigiosin induces the proapoptotic gene NAG-1 via glycogen synthase kinase-3{beta} activity in human breast cancer cells Mol. Cancer Ther., January 1, 2007; 6(1): 362 - 369. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Martinez, T. Sali, R. Okazaki, C. Anna, M. Hollingshead, C. Hose, A. Monks, N. J. Walker, S. J. Baek, and T. E. Eling Drug-Induced Expression of Nonsteroidal Anti-Inflammatory Drug-Activated Gene/Macrophage Inhibitory Cytokine-1/Prostate-Derived Factor, a Putative Tumor Suppressor, Inhibits Tumor Growth J. Pharmacol. Exp. Ther., August 1, 2006; 318(2): 899 - 906. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. R. Bauskin, D. A. Brown, T. Kuffner, H. Johnen, X. W. Luo, M. Hunter, and S. N. Breit Role of macrophage inhibitory cytokine-1 in tumorigenesis and diagnosis of cancer. Cancer Res., May 15, 2006; 66(10): 4983 - 4986. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-H. Lee, K. Yamaguchi, J.-S. Kim, T. E. Eling, S. Safe, Y. Park, and S. J. Baek Conjugated linoleic acid stimulates an anti-tumorigenic protein NAG-1 in an isomer specific manner Carcinogenesis, May 1, 2006; 27(5): 972 - 981. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Yamaguchi, S.-H. Lee, J.-S. Kim, J. Wimalasena, S. Kitajima, and S. J. Baek Activating Transcription Factor 3 and Early Growth Response 1 Are the Novel Targets of LY294002 in a Phosphatidylinositol 3-Kinase-Independent Pathway Cancer Res., February 15, 2006; 66(4): 2376 - 2384. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Chintharlapalli, S. Papineni, S. J. Baek, S. Liu, and S. Safe 1,1-Bis(3'-indolyl)-1-(p-substitutedphenyl)methanes Are Peroxisome Proliferator-Activated Receptor {gamma} Agonists but Decrease HCT-116 Colon Cancer Cell Survival through Receptor-Independent Activation of Early Growth Response-1 and Nonsteroidal Anti-Inflammatory Drug-Activated Gene-1 Mol. Pharmacol., December 1, 2005; 68(6): 1782 - 1792. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. G. Bottone Jr., Y. Moon, B. Alston-Mills, and T. E. Eling Transcriptional Regulation of Activating Transcription Factor 3 Involves the Early Growth Response-1 Gene J. Pharmacol. Exp. Ther., November 1, 2005; 315(2): 668 - 677. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Moon, F. G. Bottone Jr., M. F. McEntee, and T. E. Eling Suppression of tumor cell invasion by cyclooxygenase inhibitors is mediated by thrombospondin-1 via the early growth response gene Egr-1 Mol. Cancer Ther., October 1, 2005; 4(10): 1551 - 1558. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-H. Kim, K. Yamaguchi, S.-H. Lee, P. K. Tithof, G. S. Sayler, J.-H. Yoon, and S. J. Baek Evaluation of Polycyclic Aromatic Hydrocarbons in the Activation of Early Growth Response-1 and Peroxisome Proliferator Activated Receptors Toxicol. Sci., May 1, 2005; 85(1): 585 - 593. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-S. Kim, S. J. Baek, T. Sali, and T. E. Eling The conventional nonsteroidal anti-inflammatory drug sulindac sulfide arrests ovarian cancer cell growth via the expression of NAG-1/MIC-1/GDF-15 Mol. Cancer Ther., March 1, 2005; 4(3): 487 - 493. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
