|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 281, Issue 18, 12210-12217, May 5, 2006
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
NFAT Induces Breast Cancer Cell Invasion by Promoting the Induction of Cyclooxygenase-2*
From the Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215
The NFAT (nuclear factor of activated T cells) family of transcription factors plays a fundamental role in the transcriptional regulation of the immune response. However, NFATs are ubiquitously expressed, and recent evidence points to their important functions in human epithelial cells and carcinomas. Specifically, NFAT has been shown to be active in human breast and colon carcinoma cells and to promote their invasion through Matrigel. The mechanisms by which NFAT promotes invasion have not been defined. To identify NFAT target genes that induce carcinoma invasion, we have established stable breast cancer cell lines that inducibly express transcriptionally active NFAT. Gene expression profiling by cDNA microarray of cells induced to express NFAT revealed up-regulation of cyclooxygenase-2 (COX-2). Increased NFAT expression and activity induced COX-2 expression as well as prostaglandin E2 synthesis. This induction was more prominent when NFAT was activated by phorbol 12-myristate 13-acetate and calcium ionophore ionomycin and was blocked by the NFAT antagonist cyclosporin A. Breast cancer cells with elevated COX-2 expression showed increased invasion through Matrigel, and this was reduced in cells treated with COX-2 inhibitors. Conversely, loss of NFAT1 protein expression using small interfering RNA led to a reduction in COX-2 transcription and reduced invasion. Similarly, Matrigel invasion was reduced in cells in which COX-2 expression was reduced using specific siRNA. These findings demonstrate that NFAT promotes breast cancer cell invasion through the induction of COX-2 and the synthesis of prostaglandins.
Received for publication, January 9, 2006 , and in revised form, February 2, 2006.
* This work was supported by National Institutes of Health Grants CA96710 (to A. T.) and T32HL007893 (G. K. Y.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 To whom correspondence should be addressed: Dept. of Pathology, Beth Israel Deaconess Medical Center, 330 Brookline Ave., RN-237, Boston, MA 02215. Tel.: 617-667-8535; Fax: 617-667-3616; E-mail: atoker{at}bidmc.harvard.edu.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  H. J. Cho, K. E. Baek, S.-M. Park, I.-K. Kim, Y.-L. Choi, H.-J. Cho, I.-K. Nam, E. M. Hwang, J.-Y. Park, J. Y. Han, et al. RhoGDI2 Expression Is Associated with Tumor Growth and Malignant Progression of Gastric Cancer Clin. Cancer Res., April 15, 2009; 15(8): 2612 - 2619. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Adinolfi, M. G. Callegari, M. Cirillo, P. Pinton, C. Giorgi, D. Cavagna, R. Rizzuto, and F. Di Virgilio Expression of the P2X7 Receptor Increases the Ca2+ Content of the Endoplasmic Reticulum, Activates NFATc1, and Protects from Apoptosis J. Biol. Chem., April 10, 2009; 284(15): 10120 - 10128. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Yoeli-Lerner, Y. R. Chin, C. K. Hansen, and A. Toker Akt/Protein Kinase B and Glycogen Synthase Kinase-3{beta} Signaling Pathway Regulates Cell Migration through the NFAT1 Transcription Factor Mol. Cancer Res., March 1, 2009; 7(3): 425 - 432. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Chen, M. Sinha, B. A. Luxon, A. R. Bresnick, and K. L. O'Connor Integrin {alpha}6{beta}4 Controls the Expression of Genes Associated with Cell Motility, Invasion, and Metastasis, Including S100A4/Metastasin J. Biol. Chem., January 16, 2009; 284(3): 1484 - 1494. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. Flockhart, B. L. Diffey, P. M. Farr, J. Lloyd, and N. J. Reynolds NFAT regulates induction of COX-2 and apoptosis of keratinocytes in response to ultraviolet radiation exposure FASEB J, December 1, 2008; 22(12): 4218 - 4227. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Safholm, J. Tuomela, J. Rosenkvist, J. Dejmek, P. Harkonen, and T. Andersson The Wnt-5a-Derived Hexapeptide Foxy-5 Inhibits Breast Cancer Metastasis In vivo by Targeting Cell Motility Clin. Cancer Res., October 15, 2008; 14(20): 6556 - 6563. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Pew, M. Zou, D. R. Brickley, and S. D. Conzen Glucocorticoid (GC)-Mediated Down-Regulation of Urokinase Plasminogen Activator Expression via the Serum and GC Regulated Kinase-1/Forkhead Box O3a Pathway Endocrinology, May 1, 2008; 149(5): 2637 - 2645. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Akimzhanov, L. Krenacs, T. Schlegel, S. Klein-Hessling, E. Bagdi, E. Stelkovics, E. Kondo, S. Chuvpilo, P. Wilke, A. Avots, et al. Epigenetic Changes and Suppression of the Nuclear Factor of Activated T Cell 1 (NFATC1) Promoter in Human Lymphomas with Defects in Immunoreceptor Signaling Am. J. Pathol., January 1, 2008; 172(1): 215 - 224. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Schunke, P. Span, H. Ronneburg, A. Dittmer, M. Vetter, H.-J. Holzhausen, E. Kantelhardt, S. Krenkel, V. Muller, F. C.G.J. Sweep, et al. Cyclooxygenase-2 Is a Target Gene of Rho GDP Dissociation Inhibitor {beta} in Breast Cancer Cells Cancer Res., November 15, 2007; 67(22): 10694 - 10702. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. R. Bush, J. M. Havens, B. M. Necela, W. Su, L. Chen, M. Yanagisawa, P. Z. Anastasiadis, R. Guerra, B. A. Luxon, and E. A. Thompson Functional Genomic Analysis Reveals Cross-talk between Peroxisome Proliferator-activated Receptor {gamma} and Calcium Signaling in Human Colorectal Cancer Cells J. Biol. Chem., August 10, 2007; 282(32): 23387 - 23401. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Stasinopoulos, D. R. O'Brien, F. Wildes, K. Glunde, and Z. M. Bhujwalla Silencing of Cyclooxygenase-2 Inhibits Metastasis and Delays Tumor Onset of Poorly Differentiated Metastatic Breast Cancer Cells Mol. Cancer Res., May 1, 2007; 5(5): 435 - 442. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Batista, D. Vaiman, J. Dausset, M. Fellous, and R. A. Veitia Potential targets of FOXL2, a transcription factor involved in craniofacial and follicular development, identified by transcriptomics PNAS, February 27, 2007; 104(9): 3330 - 3335. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. G. Maroulakou, W. Oemler, S. P. Naber, and P. N. Tsichlis Akt1 Ablation Inhibits, whereas Akt2 Ablation Accelerates, the Development of Mammary Adenocarcinomas in Mouse Mammary Tumor Virus (MMTV)-ErbB2/Neu and MMTV-Polyoma Middle T Transgenic Mice Cancer Res., January 1, 2007; 67(1): 167 - 177. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |