JBC

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


     

Originally published In Press as doi:10.1074/jbc.M003581200 on October 20, 2000

J. Biol. Chem., Vol. 276, Issue 2, 1226-1232, January 12, 2001
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
276/2/1226    most recent
M003581200v1
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 Van Putten, V.
Right arrow Articles by Nemenoff, R. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Van Putten, V.
Right arrow Articles by Nemenoff, R. A.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Induction of Cytosolic Phospholipase A2 by Oncogenic Ras Is Mediated through the JNK and ERK Pathways in Rat Epithelial Cells*

Vicki Van PuttenDagger , Zaki RefaatDagger , Christina DessevDagger , Stacy Blaine§, Marilee WickDagger , Laura ButterfieldDagger , Sun-Young Han§, Lynn E. HeasleyDagger §, and Raphael A. NemenoffDagger §

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

Mutations in ras genes have been detected with high frequency in nonsmall cell lung cancer cells (NSCLC) and contribute to transformed growth of these cells. It has previously been shown that expression of oncogenic forms of Ras in these cells is associated with elevated expression of cytosolic phospholipase A2 (cPLA2) and cyclooxygenase-2 (COX-2), resulting in high constitutive levels of prostaglandin production. To determine whether expression of constitutively active Ras is sufficient to induce expression of these enzymes in nontransformed cells, normal lung epithelial cells were transfected with H-Ras. Stable expression of H-Ras increased expression of cPLA2 and COX-2 protein. Transient transfection with H-Ras increased promoter activity for both enzymes. H-Ras expression also activated all three families of MAP kinase: ERKs, JNKs, and p38 MAP kinase. Expression of constitutively active Raf did not increase either cPLA2 or COX-2 promoter activity, but inhibition of the ERK pathway with pharmacological agents or expression of dominant negative ERK partially blocked the H-Ras-mediated induction of cPLA2 promoter activity. Expression of dominant negative JNK kinases decreased cPLA2 promoter activity in NSCLC cell lines and inhibited H-Ras-mediated induction in normal epithelial cells, whereas expression of constructs encoding constitutively active JNKs increased promoter activity. Inhibition of p38 MAP kinase or NF-kappa B had no effect on cPLA2 expression. Truncational analysis revealed that the region of the cPLA2 promoter from -58 to +12 contained sufficient elements to mediate H-Ras induction. We conclude that expression of oncogenic forms of Ras directly increases cPLA2 expression in normal epithelial cells through activation of the JNK and ERK pathways.

* This work was supported by National Cancer Institute Grant SPORE 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: Division 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.
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 Mol. Pharmacol.Home page
Y. Bren-Mattison, A. M. Meyer, V. Van Putten, H. Li, K. Kuhn, R. Stearman, M. Weiser-Evans, R. A. Winn, L. E. Heasley, and R. A. Nemenoff
Antitumorigenic Effects of Peroxisome Proliferator-Activated Receptor-{gamma} in Non-Small-Cell Lung Cancer Cells Are Mediated by Suppression of Cyclooxygenase-2 via Inhibition of Nuclear Factor-{kappa}B
Mol. Pharmacol., March 1, 2008; 73(3): 709 - 717.
[Abstract] [Full Text] [PDF]

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
 Proc. Natl. Acad. Sci. USAHome page
F. Hohla, A. V. Schally, C. A. Kanashiro, S. Buchholz, B. Baker, C. Kannadka, A. Moder, E. Aigner, C. Datz, and G. Halmos
Growth inhibition of non-small-cell lung carcinoma by BN/GRP antagonist is linked with suppression of K-Ras, COX-2, and pAkt
PNAS, November 20, 2007; 104(47): 18671 - 18676.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
F. Hohla, A. V. Schally, K. Szepeshazi, J. L. Varga, S. Buchholz, F. Koster, E. Heinrich, G. Halmos, F. G. Rick, C. Kannadka, et al.
Synergistic inhibition of growth of lung carcinomas by antagonists of growth hormone-releasing hormone in combination with docetaxel
PNAS, September 26, 2006; 103(39): 14513 - 14518.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
S.-H. Kim, Y.-H. Kim, K.-J. Shin, Y.-S. Oh, C. S. Lee, K.-O. Kang, S. H. Ryu, and P.-G. Suh
2,2',4,6,6'-Pentachlorobiphenyl-Induced Apoptosis Is Limited by Cyclooxygenase-2 Induction
Toxicol. Sci., February 1, 2005; 83(2): 397 - 404.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
M. Wick, G. Hurteau, C. Dessev, D. Chan, M. W. Geraci, R. A. Winn, L. E. Heasley, and R. A. Nemenoff
Peroxisome Proliferator-Activated Receptor-gamma Is a Target of Nonsteroidal Anti-Inflammatory Drugs Mediating Cyclooxygenase-Independent Inhibition of Lung Cancer Cell Growth
Mol. Pharmacol., November 1, 2002; 62(5): 1207 - 1214.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. A. Blaine, M. Wick, C. Dessev, and R. A. Nemenoff
Induction of cPLA2 in Lung Epithelial Cells and Non-small Cell Lung Cancer Is Mediated by Sp1 and c-Jun
J. Biol. Chem., November 9, 2001; 276(46): 42737 - 42743.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
R. Nijhara, S. S. Jana, S. K. Goswami, A. Rana, S. S. Majumdar, V. Kumar, and D. P. Sarkar
Sustained Activation of Mitogen-Activated Protein Kinases and Activator Protein 1 by the Hepatitis B Virus X Protein in Mouse Hepatocytes In Vivo
J. Virol., November 1, 2001; 75(21): 10348 - 10358.
[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 
Copyright © 2001 by the American Society for Biochemistry and Molecular Biology.