Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Prostaglandin E2 Regulates Cell Migration via the Intracellular Activation of the Epidermal Growth Factor Receptor*
F. Gregory Buchanan ,
Dingzhi Wang ,
Francesca Bargiacchi , and
Raymond N. DuBois ¶ || **
Department of Medicine and the
Departments of ¶Cell and Developmental Biology
and Cancer Biology and the ||Vanderbilt-Ingram
Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee
37232 and Molecular Oncology, Genentech Inc.,
San Francisco, California 94080
Abstract:
Over the past decade cyclooxygenase-2-derived prostaglandinshave been
implicated in the development and progression ofmany types of cancer.
Recently our laboratory has shown thattreatment with prostaglandin
E2 (PGE2) induces increased proliferation,migration,
and invasiveness of colorectal carcinoma cells (Sheng,H., Shao, J.,
Washington, M. K., and DuBois, R. N. (2001) J.Biol. Chem. 276,
18075–18081). The stimulatory effectsof PGE2 were dependent
upon the activation of the phosphatidylinositol3-kinase/Akt pathway. However,
the exact signaling cascaderesponsible for phosphatidylinositol 3-kinase/Akt
activationby PGE2 remains poorly defined. In the present study, we
demonstratethat the PGE2-induced migration and invasion occurs via
rapidtransactivation and phosphorylation of the epidermal growthfactor
receptor (EGFR). Within minutes following treatment,PGE2 induces
the activation of Akt. This effect was completelyabolished by EGFR-specific
tyrosine kinase inhibitors providingevidence for the role of the EGFR in this
response. The rapidtransactivation of the EGFR occurs via an intracellular
Src-mediatedevent but not through the release of an extracellular epidermal
growth factor-like ligand. EGFR transactivation was also observedin
vivo by the direct comparison of normal and malignant humancolorectal
samples. These results suggest that in developingcolonic carcinomas, the
early effects of cyclooxygenase-2-derivedPGE2 are in part mediated
by the EGFR, and this transactivationis responsible for subsequent
down-stream effects includingthe stimulation of cell migration and
invasion.
Received for publication March 11, 2003.
Revision received June 23, 2003.
* This work was supported in part by United States Public HealthServices
Grants DK 47297, P30CA-68485, DK 62112, and PO1CA-77839(to R. N. D.). The
costs of publication of this article weredefrayed in part by the payment of
page charges. This articlemust therefore be hereby marked
"advertisement" in accordancewith 18 U.S.C. Section 1734
solely to indicate this fact.
**
Mina C. Wallace Professor and supported by the T. J. Martell Foundation and
National Colon Cancer Research Association. To whom correspondence should be
addressed: Dept. of Medicine/GI, MCN C-2104, Vanderbilt University Medical
Center, 1161 21st Ave. S., Nashville, TN 37232-2279. Tel.: 615-343-4747; Fax:
615-343-6229; E-mail:
raymond.dubois{at}vanderbilt.edu.
The editors suggest the following Related Resources on Science sites:
TGF-{beta} Effects on Prostate Cancer Cell Migration and Invasion Are Mediated by PGE2 through Activation of PI3K/AKT/mTOR Pathway.
B. T. Vo, D. Morton Jr., S. Komaragiri, A. C. Millena, C. Leath, and S. A. Khan (2013)
Endocrinology
154, 1768-1779
|Abstract »|Full Text »|PDF »
Selective Inhibition of Prostaglandin E2 Receptors EP2 and EP4 Inhibits Adhesion of Human Endometriotic Epithelial and Stromal Cells Through Suppression of Integrin-Mediated Mechanisms.
J. Lee, S. K. Banu, R. C. Burghardt, A. Starzinski-Powitz, and J. A. Arosh (2013)
Biol Reprod
88, 77
|Abstract »|Full Text »|PDF »
Preventative topical diclofenac treatment differentially decreases tumor burden in male and female Skh-1 mice in a model of UVB-induced cutaneous squamous cell carcinoma.
E. M. Burns, K. L. Tober, J. A. Riggenbach, J. S. Schick, K. N. Lamping, D. F. Kusewitt, G. S. Young, and T. M. Oberyszyn (2013)
Carcinogenesis
34, 370-377
|Abstract »|Full Text »|PDF »
Cytochrome P450 2S1 Depletion Enhances Cell Proliferation and Migration in Bronchial Epithelial Cells, in Part, through Modulation of Prostaglandin E2 Synthesis.
T. W. Madanayake, T. P. Fidler, T. M. Fresquez, N. Bajaj, and A. M. Rowland (2012)
Drug Metab. Dispos.
40, 2119-2125
|Abstract »|Full Text »|PDF »
Adenosine triphosphate regulates NADPH oxidase activity leading to hydrogen peroxide production and COX-2/PGE2 expression in A549 cells.
C.-C. Lin, I.-T. Lee, W.-L. Wu, W.-N. Lin, and C.-M. Yang (2012)
Am J Physiol Lung Cell Mol Physiol
303, L401-L412
|Abstract »|Full Text »|PDF »
Omega-3 polyunsaturated fatty acids for the treatment and prevention of colorectal cancer.
Airway Epithelial Epidermal Growth Factor Receptor Mediates Hogbarn Dust-Induced Cytokine Release but Not Ca2+ Response.
P. R. Dodmane, N. A. Schulte, A. J. Heires, H. Band, D. J. Romberger, and M. L. Toews (2011) 45, 882-888
|Abstract »|Full Text »|PDF »
Deletion of cyclooxygenase 2 in mouse mammary epithelial cells delays breast cancer onset through augmentation of type 1 immune responses in tumors.
N. Markosyan, E. P. Chen, V. N. Ndong, Y. Yao, C. J. Sterner, L. A. Chodosh, J. A. Lawson, G. A. FitzGerald, and E. M. Smyth (2011)
Carcinogenesis
32, 1441-1449
|Abstract »|Full Text »|PDF »
V. R. Holla, H. Wu, Q. Shi, D. G. Menter, and R. N. DuBois (2011)
J. Biol. Chem.
286, 30003-30009
|Abstract »|Full Text »|PDF »
TNF transactivation of EGFR stimulates cytoprotective COX-2 expression in gastrointestinal epithelial cells.
S. S. Hobbs, J. A. Goettel, D. Liang, F. Yan, K. L. Edelblum, M. R. Frey, M. T. Mullane, and D. B. Polk (2011)
Am J Physiol Gastrointest Liver Physiol
301, G220-G229
|Abstract »|Full Text »|PDF »
Consequences of Epidermal Growth Factor Receptor (ErbB1) Loss for Vascular Smooth Muscle Cells From Mice With Targeted Deletion of ErbB1.
B. Schreier, M. Dohler, S. Rabe, B. Schneider, G. Schwerdt, S. Ruhs, M. Sibilia, M. Gotthardt, M. Gekle, and C. Grossmann (2011)
Arterioscler Thromb Vasc Biol
31, 1643-1652
|Abstract »|Full Text »|PDF »
Enforced Expression of miR-101 Inhibits Prostate Cancer Cell Growth by Modulating the COX-2 Pathway In Vivo.
Y. Hao, X. Gu, Y. Zhao, S. Greene, W. Sha, D. T. Smoot, J. Califano, T.- C. Wu, and X. Pang (2011)
Cancer Prevention Research
4, 1073-1083
|Abstract »|Full Text »|PDF »
The Prostaglandin E2 Receptor, EP2, Stimulates Keratinocyte Proliferation in Mouse Skin by G Protein-dependent and {beta}-Arrestin1-dependent Signaling Pathways.
K.-S. Chun, H.-C. Lao, and R. Langenbach (2010)
J. Biol. Chem.
285, 39672-39681
|Abstract »|Full Text »|PDF »
Brain Fatty Acid-binding Protein and {omega}-3/{omega}-6 Fatty Acids: MECHANISTIC INSIGHT INTO MALIGNANT GLIOMA CELL MIGRATION.
R. Mita, M. J. Beaulieu, C. Field, and R. Godbout (2010)
J. Biol. Chem.
285, 37005-37015
|Abstract »|Full Text »|PDF »
Prostaglandin E Receptor EP1 Suppresses Breast Cancer Metastasis and Is Linked to Survival Differences and Cancer Disparities.
X. Ma, N. Kundu, O. B. Ioffe, O. Goloubeva, R. Konger, C. Baquet, P. Gimotty, J. Reader, and A. M. Fulton (2010)
Mol. Cancer Res.
8, 1310-1318
|Abstract »|Full Text »|PDF »
Amphiregulin Promotes Intestinal Epithelial Regeneration: Roles of Intestinal Subepithelial Myofibroblasts.
Gonadotropins Induce Tumor Cell Migration and Invasion by Increasing Cyclooxygenases Expression and Prostaglandin E2 Production in Human Ovarian Cancer Cells.
M.-T. Lau, A. S. T. Wong, and P. C. K. Leung (2010)
Endocrinology
151, 2985-2993
|Abstract »|Full Text »|PDF »
Phosphatase and Tensin Homologue on Chromosome 10 (PTEN) Directs Prostaglandin E2-mediated Fibroblast Responses via Regulation of E Prostanoid 2 Receptor Expression.
R. L. Sagana, M. Yan, A. M. Cornett, J. L. Tsui, D. A. Stephenson, S. K. Huang, B. B. Moore, M. N. Ballinger, J. Melonakos, C. D. Kontos, et al. (2009)
J. Biol. Chem.
284, 32264-32271
|Abstract »|Full Text »|PDF »
Elevated Levels of Urinary Prostaglandin E Metabolite Indicate a Poor Prognosis in Ever Smoker Head and Neck Squamous Cell Carcinoma Patients.
V. D. Kekatpure, J. O. Boyle, X. K. Zhou, A. J. Duffield-Lillico, N. D. Gross, N. Y. Lee, K. Subbaramaiah, J. D. Morrow, G. Milne, S. M. Lippman, et al. (2009)
Cancer Prevention Research
2, 957-965
|Abstract »|Full Text »|PDF »
Experimental cancer therapy using restoration of NAD+-linked 15-hydroxyprostaglandin dehydrogenase expression.
L. N. Kaliberova, S. A. Kusmartsev, V. Krendelchtchikova, C. R. Stockard, W. E. Grizzle, D. J. Buchsbaum, and S. A. Kaliberov (2009)
Mol. Cancer Ther.
8, 3130-3139
|Abstract »|Full Text »|PDF »
HGF/Met signalling promotes PGE2 biogenesis via regulation of COX-2 and 15-PGDH expression in colorectal cancer cells.
A. E. Moore, A. Greenhough, H. R. Roberts, D. J. Hicks, H. A. Patsos, A. C. Williams, and C. Paraskeva (2009)
Carcinogenesis
30, 1796-1804
|Abstract »|Full Text »|PDF »
The prostaglandin receptor EP2 activates multiple signaling pathways and {beta}-arrestin1 complex formation during mouse skin papilloma development.
K.-S. Chun, H.-C. Lao, C. S. Trempus, M. Okada, and R. Langenbach (2009)
Carcinogenesis
30, 1620-1627
|Abstract »|Full Text »|PDF »
Resistance to chemotherapy and hormone therapy in endometrial cancer.
Epidermal Growth Factor-activated Aryl Hydrocarbon Receptor Nuclear Translocator/HIF-1{beta} Signal Pathway Up-regulates Cyclooxygenase-2 Gene Expression Associated with Squamous Cell Carcinoma.
K.-Y. Chang, M.-R. Shen, M.-Y. Lee, W.-L. Wang, W.-C. Su, W.-C. Chang, and B.-K. Chen (2009)
J. Biol. Chem.
284, 9908-9916
|Abstract »|Full Text »|PDF »
The COX-2/PGE2 pathway: key roles in the hallmarks of cancer and adaptation to the tumour microenvironment.
A. Greenhough, H. J.M. Smartt, A. E. Moore, H. R. Roberts, A. C. Williams, C. Paraskeva, and A. Kaidi (2009)
Carcinogenesis
30, 377-386
|Abstract »|Full Text »|PDF »
Lipopolysaccharide Initiates a Positive Feedback of Epidermal Growth Factor Receptor Signaling by Prostaglandin E2 in Human Biliary Carcinoma Cells.
L. Finzi, M. X. G. Shao, F. Paye, C. Housset, and J. A. Nadel (2009)
J. Immunol.
182, 2269-2276
|Abstract »|Full Text »|PDF »
A plant flavonoid fisetin induces apoptosis in colon cancer cells by inhibition of COX2 and Wnt/EGFR/NF-{kappa}B-signaling pathways.
Y. Suh, F. Afaq, J. J. Johnson, and H. Mukhtar (2009)
Carcinogenesis
30, 300-307
|Abstract »|Full Text »|PDF »
K. Subbaramaiah, R. Benezra, C. Hudis, and A. J. Dannenberg (2008)
J. Biol. Chem.
283, 33955-33968
|Abstract »|Full Text »|PDF »
The Aryl Hydrocarbon Receptor Attenuates Tobacco Smoke-induced Cyclooxygenase-2 and Prostaglandin Production in Lung Fibroblasts through Regulation of the NF-{kappa}B Family Member RelB.
C. J. Baglole, S. B. Maggirwar, T. A. Gasiewicz, T. H. Thatcher, R. P. Phipps, and P. J. Sime (2008)
J. Biol. Chem.
283, 28944-28957
|Abstract »|Full Text »|PDF »
Prostaglandin E2 Regulates Tumor Angiogenesis in Prostate Cancer.
S. Jain, G. Chakraborty, R. Raja, S. Kale, and G. C. Kundu (2008)
Cancer Res.
68, 7750-7759
|Abstract »|Full Text »|PDF »
PGE2 induces angiogenesis via MT1-MMP-mediated activation of the TGF{beta}/Alk5 signaling pathway.
A. Alfranca, J. M. Lopez-Oliva, L. Genis, D. Lopez-Maderuelo, I. Mirones, D. Salvado, A. J. Quesada, A. G. Arroyo, and J. M. Redondo (2008)
Blood
112, 1120-1128
|Abstract »|Full Text »|PDF »
Regulation of Prostaglandin Transporters in Colorectal Neoplasia.
V. R. Holla, M. G. Backlund, P. Yang, R. A. Newman, and R. N. DuBois (2008)
Cancer Prevention Research
1, 93-99
|Abstract »|Full Text »|PDF »
CUGBP2 downregulation by prostaglandin E2 protects colon cancer cells from radiation-induced mitotic catastrophe.
G. Natarajan, S. Ramalingam, I. Ramachandran, R. May, L. Queimado, C. W. Houchen, and S. Anant (2008)
Am J Physiol Gastrointest Liver Physiol
294, G1235-G1244
|Abstract »|Full Text »|PDF »
Cyclooxygenase-2 Regulates Survival, Migration, and Invasion of Human Endometriotic Cells through Multiple Mechanisms.
S. K. Banu, J. Lee, V. O. Speights Jr., A. Starzinski-Powitz, and J. A. Arosh (2008)
Endocrinology
149, 1180-1189
|Abstract »|Full Text »|PDF »
Cyclooxygenase-2 Inhibition Inhibits c-Met Kinase Activity and Wnt Activity in Colon Cancer.
J. B. Tuynman, L. Vermeulen, E. M. Boon, K. Kemper, A. H. Zwinderman, M. P. Peppelenbosch, and D. J. Richel (2008)
Cancer Res.
68, 1213-1220
|Abstract »|Full Text »|PDF »
Prostaglandin E2 Regulates Angiogenesis via Activation of Fibroblast Growth Factor Receptor-1.
F. Finetti, R. Solito, L. Morbidelli, A. Giachetti, M. Ziche, and S. Donnini (2008)
J. Biol. Chem.
283, 2139-2146
|Abstract »|Full Text »|PDF »
Prostaglandin E2 Mediates IL-1 -Related Fibroblast Mitogenic Effects in Acute Lung Injury through Differential Utilization of Prostanoid Receptors.
K. E. White, Q. Ding, B. B. Moore, M. Peters-Golden, L. B. Ware, M. A. Matthay, and M. A. Olman (2008)
J. Immunol.
180, 637-646
|Abstract »|Full Text »|PDF »
Targeting Cyclooxygenase-2 and the Epidermal Growth Factor Receptor for the Prevention and Treatment of Intestinal Cancer.
F. G. Buchanan, V. Holla, S. Katkuri, P. Matta, and R. N. DuBois (2007)
Cancer Res.
67, 9380-9388
|Abstract »|Full Text »|PDF »
PGE2 inhibits apoptosis in human adenocarcinoma Caco-2 cell line through Ras-PI3K association and cAMP-dependent kinase A activation.
V. Leone, A. di Palma, P. Ricchi, F. Acquaviva, M. Giannouli, A. M. Di Prisco, F. Iuliano, and A. M. Acquaviva (2007)
Am J Physiol Gastrointest Liver Physiol
293, G673-G681
|Abstract »|Full Text »|PDF »
Expansion of Human T Regulatory Type 1 Cells in the Microenvironment of Cyclooxygenase 2 Overexpressing Head and Neck Squamous Cell Carcinoma.
C. Bergmann, L. Strauss, R. Zeidler, S. Lang, and T. L. Whiteside (2007)
Cancer Res.
67, 8865-8873
|Abstract »|Full Text »|PDF »
EP2 prostanoid receptor promotes squamous cell carcinoma growth through epidermal growth factor receptor transactivation and iNOS and ERK1/2 pathways.
S. Donnini, F. Finetti, R. Solito, E. Terzuoli, A. Sacchetti, L. Morbidelli, P. Patrignani, and M. Ziche (2007)
FASEB J
21, 2418-2430
|Abstract »|Full Text »|PDF »
Phosphatidylinositol 3-kinase is involved in prostaglandin E2-mediated murine duodenal bicarbonate secretion.
B.-G. Tuo, G.-R. Wen, and U. Seidler (2007)
Am J Physiol Gastrointest Liver Physiol
293, G279-G287
|Abstract »|Full Text »|PDF »
Dissociation between the translocation and the activation of Akt in fMLP-stimulated human neutrophils--effect of prostaglandin E2.
C. Burelout, P. H. Naccache, and S. G. Bourgoin (2007)
J. Leukoc. Biol.
81, 1523-1534
|Abstract »|Full Text »|PDF »
Cyclooxygenase-2 Transcription Is Regulated by Human Papillomavirus 16 E6 and E7 Oncoproteins: Evidence of a Corepressor/Coactivator Exchange.
TNF-{alpha} induces MMP-9 expression via activation of Src/EGFR, PDGFR/PI3K/Akt cascade and promotion of NF-{kappa}B/p300 binding in human tracheal smooth muscle cells.
C.-W. Lee, C.-C. Lin, W.-N. Lin, K.-C. Liang, S.-F. Luo, C.-B. Wu, S.-W. Wang, and C.-M. Yang (2007)
Am J Physiol Lung Cell Mol Physiol
292, L799-L812
|Abstract »|Full Text »|PDF »
Microsomal Prostaglandin E Synthase-1 Deficiency Is Associated with Elevated Peroxisome Proliferator-activated Receptor {gamma}: REGULATION BY PROSTAGLANDIN E2 VIA THE PHOSPHATIDYLINOSITOL 3-KINASE AND AKT PATHWAY.
M. Kapoor, F. Kojima, M. Qian, L. Yang, and L. J. Crofford (2007)
J. Biol. Chem.
282, 5356-5366
|Abstract »|Full Text »|PDF »
Seminal plasma and prostaglandin E2 up-regulate fibroblast growth factor 2 expression in endometrial adenocarcinoma cells via E-series prostanoid-2 receptor-mediated transactivation of the epidermal growth factor receptor and extracellular signal-regulated kinase pathway.
S. Battersby, K.J. Sales, A.R. Williams, R.A. Anderson, S. Gardner, and H.N. Jabbour (2007)
Hum. Reprod.
22, 36-44
|Abstract »|Full Text »|PDF »
Cross-talk between G Protein-Coupled Receptor and Epidermal Growth Factor Receptor Signaling Pathways Contributes to Growth and Invasion of Head and Neck Squamous Cell Carcinoma.
S. M. Thomas, N. E. Bhola, Q. Zhang, S. C. Contrucci, A. L. Wentzel, M. L. Freilino, W. E. Gooding, J. M. Siegfried, D. C. Chan, and J. R. Grandis (2006)
Cancer Res.
66, 11831-11839
|Abstract »|Full Text »|PDF »
Cyclooxygenase-2 and Colorectal Cancer Chemoprevention: The {beta}-Catenin Connection.
M. D. Castellone, H. Teramoto, and J. S. Gutkind (2006)
Cancer Res.
66, 11085-11088
|Abstract »|Full Text »|PDF »
Azoxymethane protects intestinal stem cells and reduces crypt epithelial mitosis through a COX-1-dependent mechanism.
T. E. Riehl, R. J. George, M. A. Sturmoski, R. May, B. Dieckgraefe, S. Anant, and C. W. Houchen (2006)
Am J Physiol Gastrointest Liver Physiol
291, G1062-G1070
|Abstract »|Full Text »|PDF »
Targeting Prostaglandin E EP Receptors to Inhibit Metastasis..
Effect of Simultaneous Inhibition of Epidermal Growth Factor Receptor and Cyclooxygenase-2 in HER-2/Neu-Positive Breast Cancer..
S. Lanza-Jacoby, R. Burd, F. E. Rosato Jr., K. McGuire, J. Little, N. Nougbilly, and S. Miller (2006)
Clin. Cancer Res.
12, 6161-6169
|Abstract »|Full Text »|PDF »
Host and Direct Antitumor Effects and Profound Reduction in Tumor Metastasis with Selective EP4 Receptor Antagonism.
L. Yang, Y. Huang, R. Porta, K. Yanagisawa, A. Gonzalez, E. Segi, D. H. Johnson, S. Narumiya, and D. P. Carbone (2006)
Cancer Res.
66, 9665-9672
|Abstract »|Full Text »|PDF »
15-Hydroxyprostaglandin dehydrogenase is an in vivo suppressor of colon tumorigenesis.
S.-J. Myung, R. M. Rerko, M. Yan, P. Platzer, K. Guda, A. Dotson, E. Lawrence, A. J. Dannenberg, A. K. Lovgren, G. Luo, et al. (2006)
PNAS
103, 12098-12102
|Abstract »|Full Text »|PDF »
Repression of Prostaglandin Dehydrogenase by Epidermal Growth Factor and Snail Increases Prostaglandin E2 and Promotes Cancer Progression..
J. R. Mann, M. G. Backlund, F. G. Buchanan, T. Daikoku, V. R. Holla, D. W. Rosenberg, S. K. Dey, and R. N. DuBois (2006)
Cancer Res.
66, 6649-6656
|Abstract »|Full Text »|PDF »
Seminal Plasma Promotes the Expression of Tumorigenic and Angiogenic Genes in Cervical Adenocarcinoma Cells via the E-Series Prostanoid 4 Receptor.
M. Muller, K. J. Sales, A. A. Katz, and H. N. Jabbour (2006)
Endocrinology
147, 3356-3365
|Abstract »|Full Text »|PDF »
Changes in Antitumor Response in C57BL/6J-Min/+ Mice during Long-term Administration of a Selective Cyclooxygenase-2 Inhibitor..
A. M. Carothers, A. E. Moran, N. L. Cho, M. Redston, and M. M. Bertagnolli (2006)
Cancer Res.
66, 6432-6438
|Abstract »|Full Text »|PDF »
Progress in Chemoprevention Drug Development: The Promise of Molecular Biomarkers for Prevention of Intraepithelial Neoplasia and Cancer--A Plan to Move Forward.
G. J. Kelloff, S. M. Lippman, A. J. Dannenberg, C. C. Sigman, H. L. Pearce, B. J. Reid, E. Szabo, V. C. Jordan, M. R. Spitz, G. B. Mills, et al. (2006)
Clin. Cancer Res.
12, 3661-3697
|Abstract »|Full Text »|PDF »
Epidermal Growth Factor Receptor Biology in Head and Neck Cancer.
A phase I trial to determine the optimal biological dose of celecoxib when combined with erlotinib in advanced non-small cell lung cancer..
K. L. Reckamp, K. Krysan, J. D. Morrow, G. L. Milne, R. A. Newman, C. Tucker, R. M. Elashoff, S. M. Dubinett, and R. A. Figlin (2006)
Clin. Cancer Res.
12, 3381-3388
|Abstract »|Full Text »|PDF »
Prostaglandin E2 promotes cell survival of glomerular epithelial cells via the EP4 receptor.
L. Aoudjit, A. Potapov, and T. Takano (2006)
Am J Physiol Renal Physiol
290, F1534-F1542
|Abstract »|Full Text »|PDF »
Prostanoid signal transduction and gene expression in the endothelium: Role in cardiovascular diseases.
A. Alfranca, M. A. Iniguez, M. Fresno, and J. M. Redondo (2006)
Cardiovasc Res
70, 446-456
|Abstract »|Full Text »|PDF »
CXCL1 induced by prostaglandin E2 promotes angiogenesis in colorectal cancer.
D. Wang, H. Wang, J. Brown, T. Daikoku, W. Ning, Q. Shi, A. Richmond, R. Strieter, S. K. Dey, and R. N. DuBois (2006)
J. Exp. Med.
203, 941-951
|Abstract »|Full Text »|PDF »
Prostacyclin Receptor Up-Regulates the Expression of Angiogenic Genes in Human Endometrium via Cross Talk with Epidermal Growth Factor Receptor and the Extracellular Signaling Receptor Kinase 1/2 Pathway.
O. P. Milling Smith, S. Battersby, K. J. Sales, H. O. D. Critchley, and H. N. Jabbour (2006)
Endocrinology
147, 1697-1705
|Abstract »|Full Text »|PDF »
Reducing the "Risk" of Chemoprevention: Defining and Targeting High Risk--2005 AACR Cancer Research and Prevention Foundation Award Lecture..
Prostaglandin E Receptor EP4 Antagonism Inhibits Breast Cancer Metastasis..
X. Ma, N. Kundu, S. Rifat, T. Walser, and A. M. Fulton (2006)
Cancer Res.
66, 2923-2927
|Abstract »|Full Text »|PDF »
FHIT Is Up-Regulated by Inflammatory Stimuli and Inhibits Prostaglandin E2-Mediated Cancer Progression..
K. Mimori, H. Ishii, H. Nagahara, T. Sudo, K. Yamashita, H. Inoue, G. F. Barnard, and M. Mori (2006)
Cancer Res.
66, 2683-2690
|Abstract »|Full Text »|PDF »
Activation of Synoviocytes by the Secreted Phospholipase A2 Motif in the VP1-Unique Region of Parvovirus B19 Minor Capsid Protein.
J. Lu, N. Zhi, S. Wong, and K. E. Brown (2006)
The Journal of Infectious Disease
193, 582-590
|Abstract »|Full Text »|PDF »
Levels of NAD+-dependent 15-hydroxyprostaglandin dehydrogenase are reduced in inflammatory bowel disease: evidence for involvement of TNF-{alpha}.
T. Otani, K. Yamaguchi, E. Scherl, B. Du, H.-H. Tai, M. Greifer, L. Petrovic, T. Daikoku, S. K. Dey, K. Subbaramaiah, et al. (2006)
Am J Physiol Gastrointest Liver Physiol
290, G361-G368
|Abstract »|Full Text »|PDF »
Role of beta-arrestin 1 in the metastatic progression of colorectal cancer.
F. G. Buchanan, D. L. Gorden, P. Matta, Q. Shi, L. M. Matrisian, and R. N. DuBois (2006)
PNAS
103, 1492-1497
|Abstract »|Full Text »|PDF »
Cyclooxygenase-1-derived PGE2 promotes cell motility via the G-protein-coupled EP4 receptor during vertebrate gastrulation.
Y. I. Cha, S.-H. Kim, D. Sepich, F. G. Buchanan, L. Solnica-Krezel, and R. N. DuBois (2006)
Genes & Dev.
20, 77-86
|Abstract »|Full Text »|PDF »
Zoledronic acid cooperates with a cyclooxygenase-2 inhibitor and gefitinib in inhibiting breast and prostate cancer.
D. Melisi, R. Caputo, V. Damiano, R. Bianco, B. M. Veneziani, A R. Bianco, S. De Placido, F. Ciardiello, and G. Tortora (2005)
Endocr. Relat. Cancer
12, 1051-1058
|Abstract »|Full Text »|PDF »
Association between cyclooxygenase and epidermal growth factor receptor pathways in non-small cell lung cancer.
M. Ates, O. Altundag, S. Aktolga, and K. Altundag (2005)
J. Thorac. Cardiovasc. Surg.
130, 1484-1485
|Full Text »|PDF »
Interaction between epidermal growth factor receptor- and cyclooxygenase 2-mediated pathways and its implications for the chemoprevention of head and neck cancer.
M. S. Choe, X. Zhang, H. J. C. Shin, D. M. Shin, and Z. Chen (2005)
Mol. Cancer Ther.
4, 1448-1455
|Abstract »|Full Text »|PDF »
Combined Targeting of the Epidermal Growth Factor Receptor and Cyclooxygenase-2 Pathways.
S. M. Lippman, N. Gibson, K. Subbaramaiah, and A. J. Dannenberg (2005)
Clin. Cancer Res.
11, 6097-6099
|Full Text »|PDF »
Prostaglandin E2 Activates Mitogen-Activated Protein Kinase/Erk Pathway Signaling and Cell Proliferation in Non-Small Cell Lung Cancer Cells in an Epidermal Growth Factor Receptor-Independent Manner.
K. Krysan, K. L. Reckamp, H. Dalwadi, S. Sharma, E. Rozengurt, M. Dohadwala, and S. M. Dubinett (2005)
Cancer Res.
65, 6275-6281
|Abstract »|Full Text »|PDF »
Prostaglandin E2 Stimulates the {beta}-Catenin/T Cell Factor-dependent Transcription in Colon Cancer.
J. Shao, C. Jung, C. Liu, and H. Sheng (2005)
J. Biol. Chem.
280, 26565-26572
|Abstract »|Full Text »|PDF »
Cyclooxygenase-2-derived Prostaglandin E2 Promotes Human Cholangiocarcinoma Cell Growth and Invasion through EP1 Receptor-mediated Activation of the Epidermal Growth Factor Receptor and Akt.
PGE2-induced hypertrophy of cardiac myocytes involves EP4 receptor-dependent activation of p42/44 MAPK and EGFR transactivation.
M. Mendez and M. C. LaPointe (2005)
Am J Physiol Heart Circ Physiol
288, H2111-H2117
|Abstract »|Full Text »|PDF »
Prostaglandin E2 promotes migration and adhesion in hepatocellular carcinoma cells.
R. Mayoral, A. Fernandez-Martinez, L. Bosca, and P. Martin-Sanz (2005)
Carcinogenesis
26, 753-761
|Abstract »|Full Text »|PDF »
15-Hydroxyprostaglandin Dehydrogenase Is Down-regulated in Colorectal Cancer.
M. G. Backlund, J. R. Mann, V. R. Holla, F. G. Buchanan, H.-H. Tai, E. S. Musiek, G. L. Milne, S. Katkuri, and R. N. DuBois (2005)
J. Biol. Chem.
280, 3217-3223
|Abstract »|Full Text »|PDF »
Prostaglandin E2 Inhibits Fibroblast Migration by E-Prostanoid 2 Receptor-Mediated Increase in PTEN Activity.
E. S. White, R. G. Atrasz, E. G. Dickie, D. M. Aronoff, V. Stambolic, T. W. Mak, B. B. Moore, and M. Peters-Golden (2005) 32, 135-141
|Abstract »|Full Text »|PDF »
Antitumor Activity of ZD6474, a Vascular Endothelial Growth Factor-2 and Epidermal Growth Factor Receptor Small Molecule Tyrosine Kinase Inhibitor, in Combination with SC-236, a Cyclooxygenase-2 Inhibitor.
C. Tuccillo, M. Romano, T. Troiani, E. Martinelli, F. Morgillo, F. De Vita, R. Bianco, G. Fontanini, R. A. Bianco, G. Tortora, et al. (2005)
Clin. Cancer Res.
11, 1268-1276
|Abstract »|Full Text »|PDF »
Activation of the Epidermal Growth Factor Receptor by Respiratory Syncytial Virus Results in Increased Inflammation and Delayed Apoptosis.
M. M. Monick, K. Cameron, J. Staber, L. S. Powers, T. O. Yarovinsky, J. G. Koland, and G. W. Hunninghake (2005)
J. Biol. Chem.
280, 2147-2158
|Abstract »|Full Text »|PDF »
Cyclooxygenase-2 and Epidermal Growth Factor Receptor: Pharmacologic Targets for Chemoprevention.
A. J. Dannenberg, S. M. Lippman, J. R. Mann, K. Subbaramaiah, and R. N. DuBois (2005)
J. Clin. Oncol.
23, 254-266
|Abstract »|Full Text »|PDF »
Prostaglandin E2 Regulates the Complement Inhibitor CD55/Decay-accelerating Factor in Colorectal Cancer.
V. R. Holla, D. Wang, J. R. Brown, J. R. Mann, S. Katkuri, and R. N. DuBois (2005)
J. Biol. Chem.
280, 476-483
|Abstract »|Full Text »|PDF »
Identification of Nonsteroidal Anti-inflammatory Drug-activated Gene (NAG-1) as a Novel Downstream Target of Phosphatidylinositol 3-Kinase/AKT/GSK-3{beta} Pathway.
K. Yamaguchi, S.-H. Lee, T. E. Eling, and S. J. Baek (2004)
J. Biol. Chem.
279, 49617-49623
|Abstract »|Full Text »|PDF »
Endothelin-1-induced Prostaglandin E2-EP2, EP4 Signaling Regulates Vascular Endothelial Growth Factor Production and Ovarian Carcinoma Cell Invasion.
F. Spinella, L. Rosano, V. Di Castro, P. G. Natali, and A. Bagnato (2004)
J. Biol. Chem.
279, 46700-46705
|Abstract »|Full Text »|PDF »
Novel Management of Oral Cancer: A Paradigm of Predictive Oncology.
Epidermal Growth Factor and Trefoil Factor Family 2 Synergistically Trigger Chemotaxis on BEAS-2B Cells via Different Signaling Cascades.
C. E. Chwieralski, I. Schnurra, L. Thim, and W. Hoffmann (2004) 31, 528-537
|Abstract »|Full Text »|PDF »
Apc Deficiency Is Associated with Increased Egfr Activity in the Intestinal Enterocytes and Adenomas of C57BL/6J-Min/+ Mice.
A. E. Moran, D. H. Hunt, S. H. Javid, M. Redston, A. M. Carothers, and M. M. Bertagnolli (2004)
J. Biol. Chem.
279, 43261-43272
|Abstract »|Full Text »|PDF »
Opioids As Modulators of Cell Death and Survival--Unraveling Mechanisms and Revealing New Indications.
,
Dingzhi Wang 
, and
Raymond N. DuBois 
