JBC

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 QUICK SEARCH:   [advanced]


     


Originally published In Press as doi:10.1074/jbc.M107773200 on September 14, 2001

J. Biol. Chem., Vol. 276, Issue 46, 42737-42743, November 16, 2001
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
276/46/42737    most recent
M107773200v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Blaine, S. A.
Right arrow Articles by Nemenoff, R. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Blaine, S. A.
Right arrow Articles by Nemenoff, R. A.

Induction of cPLA2 in Lung Epithelial Cells and Non-small Cell Lung Cancer Is Mediated by Sp1 and c-Jun*

Stacy A. BlaineDagger , Marilee Wick§, Christina Dessev§, and Raphael A. NemenoffDagger §

From the Departments of § Medicine and Dagger  Pharmacology, University of Colorado Health Science Center, Denver, Colorado 80262

Activating mutations in ras genes are frequently associated with non-small cell lung cancer cells (NSCLC) and contribute to transformed growth in these cells. Expression of oncogenic forms of Ras in these cells is associated with increased expression and activity of cytosolic phospholipase A2 (cPLA2) and cyclooxygenase-2 (COX-2), leading to constitutively elevated levels of prostaglandin production. Expression of oncogenic Ras is sufficient to induce these enzymes in normal lung epithelial cells. We have previously reported that the JNK and ERK pathways are necessary for induction of cPLA2 and have defined a minimal region of the cPLA2 promoter from -58 to -12 that is required for Ha-Ras-mediated induction. To further characterize the cis-regulatory elements within this region involved in this response, site-directed mutagenesis was used to make mutations at various sites. Three cis-regulatory elements were identified: regions -21/-18, -37/-30, and -55/-53. Mutations in any of these elements decreased basal and Ha-Ras-induced cPLA2 promoter activity in both normal lung epithelial cells, as well as steady state promoter activity in A549 cells, with a mutation in element -21/-18 completely eliminating all promoter activity. Overexpression studies and gel shift assays indicated that Sp1 may serve as a transcription factor functionally regulating promoter activity by directly interacting with two of the cis-regulatory elements, -21/-18 and -37/-30. Expression of Ha-Ras led to induction of c-Jun protein, which showed functional cooperation with Sp1 in driving promoter activity. Additional unidentified transcription factors bound to the regions from -55/-53 and -37/-34.


* This work was supported by National Institutes of Health NCI SPORE Grant CA 58187 and National Institutes of Health Grants DK 19928 and DK 39902.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed: Div. of Renal Diseases and Hypertension, Box C-281, University of Colorado Health Sciences Center, 4200 E. Ninth Ave., Denver, CO 80262. Tel.: 303-315-6733; Fax: 303-315-4852; E-mail: raphael.nemenoff@uchsc.edu.


Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.


This article has been cited by other articles:


Home page
Nucleic Acids ResHome page
J.-H. Tsou, K.-Y. Chang, W.-C. Wang, J. T. Tseng, W.-C. Su, L.-Y. Hung, W.-C. Chang, and B.-K. Chen
Nucleolin regulates c-Jun/Sp1-dependent transcriptional activation of cPLA2{alpha} in phorbol ester-treated non-small cell lung cancer A549 cells
Nucleic Acids Res., January 17, 2008; 36(1): 217 - 227.
[Abstract] [Full Text] [PDF]


Home page
Mol. Biol. CellHome page
B.-K. Chen, C.-C. Huang, W.-C. Chang, Y.-J. Chen, U. Kikkawa, K.-i. Nakahama, I. Morita, and W.-C. Chang
PP2B-mediated Dephosphorylation of c-Jun C Terminus Regulates Phorbol Ester-induced c-Jun/Sp1 Interaction in A431 Cells
Mol. Biol. Cell, March 1, 2007; 18(3): 1118 - 1127.
[Abstract] [Full Text] [PDF]


Home page
Mol. Cell. Biol.Home page
J.-J. Hung, Y.-T. Wang, and W.-C. Chang
Sp1 Deacetylation Induced by Phorbol Ester Recruits p300 To Activate 12(S)-Lipoxygenase Gene Transcription.
Mol. Cell. Biol., March 1, 2006; 26(5): 1770 - 1785.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
G. D'Orazi, M. G. Sciulli, V. Di Stefano, S. Riccioni, M. Frattini, R. Falcioni, L. Bertario, A. Sacchi, and P. Patrignani
Homeodomain-Interacting Protein Kinase-2 Restrains Cytosolic Phospholipase A2-Dependent Prostaglandin E2 Generation in Human Colorectal Cancer Cells
Clin. Cancer Res., February 1, 2006; 12(3): 735 - 741.
[Abstract] [Full Text] [PDF]


Home page
J. Immunol.Home page
B.-C. Chen, C.-C. Yu, H.-C. Lei, M.-S. Chang, M.-J. Hsu, C.-L. Huang, M.-C. Chen, J.-R. Sheu, T.-F. Chen, T.-L. Chen, et al.
Bradykinin B2 Receptor Mediates NF-{kappa}B Activation and Cyclooxygenase-2 Expression via the Ras/Raf-1/ERK Pathway in Human Airway Epithelial Cells
J. Immunol., October 15, 2004; 173(8): 5219 - 5228.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
B.-C. Chen, Y.-S. Chang, J.-C. Kang, M.-J. Hsu, J.-R. Sheu, T.-L. Chen, C.-M. Teng, and C.-H. Lin
Peptidoglycan Induces Nuclear Factor-{kappa}B Activation and Cyclooxygenase-2 Expression via Ras, Raf-1, and ERK in RAW 264.7 Macrophages
J. Biol. Chem., May 14, 2004; 279(20): 20889 - 20897.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
H. Higuchi, A. Grambihler, A. Canbay, S. F. Bronk, and G. J. Gores
Bile Acids Up-regulate Death Receptor 5/TRAIL-receptor 2 Expression via a c-Jun N-terminal Kinase-dependent Pathway Involving Sp1
J. Biol. Chem., January 2, 2004; 279(1): 51 - 60.
[Abstract] [Full Text] [PDF]


Home page
Innate ImmunityHome page
Shuling Zhang, K. Thomas, J. C.G. Blanco, C. A. Salkowski, and S. N. Vogel
The role of the interferon regulatory factors, IRF-1 and IRF-2, in LPS-induced cyclooxygenase-2 (COX-2) expression in vivo and in vitro
Innate Immunity, October 1, 2002; 8(5): 381 - 390.
[Abstract] [PDF]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2001 by the American Society for Biochemistry and Molecular Biology.