Cancer Research Translational Medicine Conference in Israel
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
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 Stephen, R. L.
Right arrow Articles by Palmer, C. N. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Stephen, R. L.
Right arrow Articles by Palmer, C. N. A.
[Cancer Research 64, 3162-3170, May 1, 2004]
© 2004 American Association for Cancer Research

Regular Articles

Activation of Peroxisome Proliferator-Activated Receptor {delta} Stimulates the Proliferation of Human Breast and Prostate Cancer Cell Lines

Ruth L. Stephen1, Mattias C. U. Gustafsson1, Morag Jarvis1, Roger Tatoud1, Barry R. Marshall1, Deborah Knight1, Ewa Ehrenborg2, Adrian L. Harris3, C. Roland Wolf1 and Colin N. A. Palmer1

1 Biomedical Research Centre and Cancer Research United Kingdom Molecular Pharmacology Unit, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland, United Kingdom; 2 Atherosclerosis Research Unit, King Gustaf V Research Institute, Karolinska Institute, Karolinska Hospital, Stockholm, Sweden; and 3 Cancer Research United Kingdom Molecular Oncology Unit, Weatherall lnstitute of Molecular Medicine, John Radcliffe Hospital, Oxford, England, United Kingdom

The nuclear receptor peroxisome proliferator-activated receptor {delta} [PPAR{delta}/ß (NR1C2)] has been implicated in colorectal carcinogenesis by various molecular genetic observations. These observations have recently been supported by studies of activation of PPAR{delta} by pharmacological agents. Here we present the first report of the stimulation of breast and prostate cancer cell growth using PPAR{delta} selective agonists. Activation of PPAR{delta} with compound F stimulated proliferation in breast (T47D, MCF7) and prostate (LNCaP, PNT1A) cell lines, which are responsive to sex hormones. Conversely, we have found that several steroid-independent cell lines, including colon lines, were unresponsive to compound F. These findings were confirmed with an additional high-affinity PPAR{delta} agonist, GW501516. Conditional expression of PPAR{delta} in MCF7 Tet-On cells resulted in a doxycycline-enhanced response to GW501516, thus providing direct genetic evidence for the role of PPAR{delta} in the proliferative response to this drug. Activation of PPAR{delta} in T47D cells resulted in increased expression of the proliferation marker Cdk2 and also vascular endothelial growth factor {alpha} (VEGF{alpha}) and its receptor, FLT-1, thus, suggesting that PPAR{delta} may initiate an autocrine loop for cellular proliferation and possibly angiogenesis. Consistent with this hypothesis, we demonstrated a pro-proliferative effect of GW501516 on human umbilical vein endothelial cell cultures and found that GW501516 also regulated the expression of VEGF{alpha} and FLT-1 in these cells. Our observations provide the first evidence that activation of PPAR{delta} can result in increased growth in breast and prostate cancer cell lines and primary endothelial cells and supports the possibility that PPAR{delta} antagonists may be of therapeutic value in the treatment of breast and prostate cancer.




This article has been cited by other articles:


Home page
 Mol. Endocrinol.Home page
S. D. Conzen
Minireview: Nuclear Receptors and Breast Cancer
Mol. Endocrinol., October 1, 2008; 22(10): 2215 - 2228.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
J.-K. Han, H.-S. Lee, H.-M. Yang, J. Hur, S.-I. Jun, J.-Y. Kim, C.-H. Cho, G.-Y. Koh, J. M. Peters, K.-W. Park, et al.
Peroxisome Proliferator-Activated Receptor-{delta} Agonist Enhances Vasculogenesis by Regulating Endothelial Progenitor Cells Through Genomic and Nongenomic Activations of the Phosphatidylinositol 3-Kinase/Akt Pathway
Circulation, September 2, 2008; 118(10): 1021 - 1033.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
C. Gaudel, C. Schwartz, C. Giordano, N. A. Abumrad, and P. A. Grimaldi
Pharmacological activation of PPAR{beta} promotes rapid and calcineurin-dependent fiber remodeling and angiogenesis in mouse skeletal muscle
Am J Physiol Endocrinol Metab, August 1, 2008; 295(2): E297 - E304.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
S. Han, J. D. Ritzenthaler, Y. Zheng, and J. Roman
PPAR{beta}/{delta} agonist stimulates human lung carcinoma cell growth through inhibition of PTEN expression: the involvement of PI3K and NF-{kappa}B signals
Am J Physiol Lung Cell Mol Physiol, June 1, 2008; 294(6): L1238 - L1249.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
H. Sun, I. M. Berquin, R. T. Owens, J. T. O'Flaherty, and I. J. Edwards
Peroxisome Proliferator-Activated Receptor {gamma}-Mediated Up-regulation of Syndecan-1 by n-3 Fatty Acids Promotes Apoptosis of Human Breast Cancer Cells
Cancer Res., April 15, 2008; 68(8): 2912 - 2919.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
N. G. Venkata, C. S. Aung, P. J. Cabot, G. R. Monteith, and S. J. Roberts-Thomson
PPAR{alpha} and PPAR{beta} Are Differentially Affected by Ethanol and the Ethanol Metabolite Acetaldehyde in the MCF-7 Breast Cancer Cell Line
Toxicol. Sci., March 1, 2008; 102(1): 120 - 128.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
H. E. Hollingshead, M. G. Borland, A. N. Billin, T. M. Willson, F. J. Gonzalez, and J. M. Peters
Ligand activation of peroxisome proliferator-activated receptor-{beta}/{delta} (PPAR{beta}/{delta}) and inhibition of cyclooxygenase 2 (COX2) attenuate colon carcinogenesis through independent signaling mechanisms
Carcinogenesis, January 1, 2008; 29(1): 169 - 176.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
H. E. Hollingshead, R. L. Killins, M. G. Borland, E. E. Girroir, A. N. Billin, T. M. Willson, A. K. Sharma, S. Amin, F. J. Gonzalez, and J. M. Peters
Peroxisome proliferator-activated receptor- /{delta} (PPAR /{delta}) ligands do not potentiate growth of human cancer cell lines
Carcinogenesis, December 1, 2007; 28(12): 2641 - 2649.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
J. M. Hall and D. P. McDonnell
The Molecular Mechanisms Underlying the Proinflammatory Actions of Thiazolidinediones in Human Macrophages
Mol. Endocrinol., August 1, 2007; 21(8): 1756 - 1768.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
D. Genini and C. V. Catapano
Block of Nuclear Receptor Ubiquitination: A MECHANISM OF LIGAND-DEPENDENT CONTROL OF PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR {delta} ACTIVITY
J. Biol. Chem., April 20, 2007; 282(16): 11776 - 11785.
[Abstract] [Full Text] [PDF]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
L. Piqueras, A. R. Reynolds, K. M. Hodivala-Dilke, A. Alfranca, J. M. Redondo, T. Hatae, T. Tanabe, T. D. Warner, and D. Bishop-Bailey
Activation of PPAR{beta}/{delta} Induces Endothelial Cell Proliferation and Angiogenesis
Arterioscler. Thromb. Vasc. Biol., January 1, 2007; 27(1): 63 - 69.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
L. Xu, C. Han, K. Lim, and T. Wu
Cross-talk between Peroxisome Proliferator-Activated Receptor {delta} and Cytosolic Phospholipase A2{alpha}/Cyclooxygenase-2/Prostaglandin E2 Signaling Pathways in Human Hepatocellular Carcinoma Cells
Cancer Res., December 15, 2006; 66(24): 11859 - 11868.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
D. Wang, H. Wang, Y. Guo, W. Ning, S. Katkuri, W. Wahli, B. Desvergne, S. K. Dey, and R. N. DuBois
From the Cover: Crosstalk between peroxisome proliferator-activated receptor {delta} and VEGF stimulates cancer progression
PNAS, December 12, 2006; 103(50): 19069 - 19074.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
L. Xu, C. Han, and T. Wu
A Novel Positive Feedback Loop between Peroxisome Proliferator-activated Receptor-{delta} and Prostaglandin E2 Signaling Pathways for Human Cholangiocarcinoma Cell Growth
J. Biol. Chem., November 10, 2006; 281(45): 33982 - 33996.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
B. Knight, B. B. Yeap, G. C. Yeoh, and J. K. Olynyk
Inhibition of adult liver progenitor (oval) cell growth and viability by an agonist of the peroxisome proliferator activated receptor (PPAR) family member {gamma}, but not {alpha} or {delta}
Carcinogenesis, October 1, 2005; 26(10): 1782 - 1792.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
V. K.W. Wong, P. Chiu, S. S.M. Chung, L. M.C. Chow, Y.-Z. Zhao, B. B. Yang, and B. C.B. Ko
Pseudolaric Acid B, a Novel Microtubule-Destabilizing Agent That Circumvents Multidrug Resistance Phenotype and Exhibits Antitumor Activity In vivo
Clin. Cancer Res., August 15, 2005; 11(16): 6002 - 6011.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
H. Sun, I. M. Berquin, and I. J. Edwards
Omega-3 Polyunsaturated Fatty Acids Regulate Syndecan-1 Expression in Human Breast Cancer Cells
Cancer Res., May 15, 2005; 65(10): 4442 - 4447.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
D. J. Kim, I. A. Murray, A. M. Burns, F. J. Gonzalez, G. H. Perdew, and J. M. Peters
Peroxisome Proliferator-activated Receptor-{beta}/{delta} Inhibits Epidermal Cell Proliferation by Down-regulation of Kinase Activity
J. Biol. Chem., March 11, 2005; 280(10): 9519 - 9527.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
M. T. Bility, J. T. Thompson, R. H. McKee, R. M. David, J. H. Butala, J. P. Vanden Heuvel, and J. M. Peters
Activation of Mouse and Human Peroxisome Proliferator-Activated Receptors (PPARs) by Phthalate Monoesters
Toxicol. Sci., November 1, 2004; 82(1): 170 - 182.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 2004 by the American Association for Cancer Research.