|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 277, Issue 12, 9728-9735, March 22, 2002
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Departments of Human papillomavirus (HPV) is an important
etiological agent in the genesis of cervical cancer. HPV-positive
cervical tumors and human papillomavirus-positive cell lines display
increased epidermal growth factor receptor (EGFR) expression, which is
associated with increased cell proliferation. ECE16-1 cells are an
HPV-immortalized human ectocervical epithelial cell line that is a
model of HPV-associated cervical neoplasia and displays elevated EGFR
levels. In the present study, we evaluated the effects of
receptor-selective retinoid ligands on EGFR-associated signal
transduction. We show that retinoic acid receptor (RAR)-selective
ligands reduce EGFR level and the magnitude and duration of EGFR
activation in EGF-stimulated cells. These effects are reversed by
cotreatment with an RAR antagonist. To identify the mechanism, we
examined the effects of retinoid treatments on
EGF-dependent signaling. Stimulation with EGF causes a
biphasic activation of the ERK1/2 MAPK. The first peak of activation is
present at 20 min, and the second is present at 36 h. This activation subsequently leads to an increase in the cyclin D1 level and
increased cell proliferation. Simultaneous treatment with EGF and a
RAR-selective retinoid inhibits both phases of ERK1/2 activation,
completely eliminates the cyclin D1 induction, and suppresses
EGF-dependent cell proliferation. This effect is specific
as retinoid treatment does not alter the level or activity of other
EGFR-regulated kinases, including AKT and the MAPKs p38 and JNK.
Retinoid X receptor-selective ligands, in contrast, did not
regulate these responses. These results suggest that RAR
ligand-associated down-regulation of EGFR activity reduces cell
proliferation by reducing the magnitude and duration of
EGF-dependent ERK1/2 activation.
Retinoids Suppress Epidermal Growth Factor-associated Cell
Proliferation by Inhibiting Epidermal Growth Factor
Receptor-dependent ERK1/2 Activation*
,
**
Environmental Health
Sciences, § Physiology and Biophysics, and
Reproductive Biology, Case Western Reserve University School
of Medicine, Cleveland, Ohio 44106 and ¶ Retinoid Research,
Allergan Pharmaceuticals, Inc., Irvine, California 92612
*
This work was supported by a grant from Ohio Cancer
Research Associates, National Institutes of Health Grant RO-1 ES09126 (to E. A. R.), and a grant from Allergan, Inc. (to R. L. E.).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.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  S. Madonna, C. Scarponi, O. De Pita, and C. Albanesi Suppressor of cytokine signaling 1 inhibits IFN-{gamma} inflammatory signaling in human keratinocytes by sustaining ERK1/2 activation FASEB J, September 1, 2008; 22(9): 3287 - 3297. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Ishimaru, T. Komatsu, M. Kasahara, Y. Katoh-Fukui, H. Ogawa, Y. Toyama, M. Maekawa, K. Toshimori, R. A. S. Chandraratna, K.-i. Morohashi, et al. Mechanism of asymmetric ovarian development in chick embryos Development, February 15, 2008; 135(4): 677 - 685. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Kobayashi, T. Shimamura, S. Monti, U. Steidl, C. J. Hetherington, A. M. Lowell, T. Golub, M. Meyerson, D. G. Tenen, G. I. Shapiro, et al. Transcriptional Profiling Identifies Cyclin D1 as a Critical Downstream Effector of Mutant Epidermal Growth Factor Receptor Signaling Cancer Res., December 1, 2006; 66(23): 11389 - 11398. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Di Girolamo, D. Wakefield, and M. T. Coroneo UVB-Mediated Induction of Cytokines and Growth Factors in Pterygium Epithelial Cells Involves Cell Surface Receptors and Intracellular Signaling. Invest. Ophthalmol. Vis. Sci., June 1, 2006; 47(6): 2430 - 2437. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Liu, D. Hartwig, S. Harloff, P. Herminghaus, T. Wedel, K. Kasper, and G. Geerling Corneal epitheliotrophic capacity of three different blood-derived preparations. Invest. Ophthalmol. Vis. Sci., June 1, 2006; 47(6): 2438 - 2444. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. H. Dragnev, W. J. Petty, S. Shah, A. Biddle, N. B. Desai, V. Memoli, J. R. Rigas, and E. Dmitrovsky Bexarotene and Erlotinib for Aerodigestive Tract Cancer J. Clin. Oncol., December 1, 2005; 23(34): 8757 - 8764. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Y. Park, A. Dillard, E. A. Williams, E. T. Wilder, M. R. Pepper, and M. A. Lane Retinol Inhibits the Growth of All-Trans-Retinoic Acid-Sensitive and All-Trans-Retinoic Acid-Resistant Colon Cancer Cells through a Retinoic Acid Receptor-Independent Mechanism Cancer Res., November 1, 2005; 65(21): 9923 - 9933. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. M. Monick, K. Cameron, J. Staber, L. S. Powers, T. O. Yarovinsky, J. G. Koland, and G. W. Hunninghake Activation of the Epidermal Growth Factor Receptor by Respiratory Syncytial Virus Results in Increased Inflammation and Delayed Apoptosis J. Biol. Chem., January 21, 2005; 280(3): 2147 - 2158. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. J. Petty, K. H. Dragnev, V. A. Memoli, Y. Ma, N. B. Desai, A. Biddle, T. H. Davis, W. C. Nugent, N. Memoli, M. Hamilton, et al. Epidermal Growth Factor Receptor Tyrosine Kinase Inhibition Represses Cyclin D1 in Aerodigestive Tract Cancers Clin. Cancer Res., November 15, 2004; 10(22): 7547 - 7554. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. F. Sah, S. Balasubramanian, R. L. Eckert, and E. A. Rorke Epigallocatechin-3-gallate Inhibits Epidermal Growth Factor Receptor Signaling Pathway: EVIDENCE FOR DIRECT INHIBITION OF ERK1/2 AND AKT KINASES J. Biol. Chem., March 26, 2004; 279(13): 12755 - 12762. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Shimizu, M. Suzui, A. Deguchi, J. T. E. Lim, and I. B. Weinstein Effects of Acyclic Retinoid on Growth, Cell Cycle Control, Epidermal Growth Factor Receptor Signaling, and Gene Expression in Human Squamous Cell Carcinoma Cells Clin. Cancer Res., February 1, 2004; 10(3): 1130 - 1140. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Lango, A. L. Wentzel, J. I. Song, S. Xi, D. E. Johnson, W. W. Lamph, L. Miller, and J. R. Grandis Responsiveness to the Retinoic Acid Receptor-selective Retinoid LGD1550 Correlates with Abrogation of Transforming Growth Factor {alpha}/Epidermal Growth Factor Receptor Autocrine Signaling in Head and Neck Squamous Carcinoma Cells Clin. Cancer Res., September 15, 2003; 9(11): 4205 - 4213. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Matsushima-Nishiwaki, M. Okuno, Y. Takano, S. Kojima, S. L. Friedman, and H. Moriwaki Molecular mechanism for growth suppression of human hepatocellular carcinoma cells by acyclic retinoid Carcinogenesis, August 1, 2003; 24(8): 1353 - 1359. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. N. Gushwa, D. Hayashi, A. Kemper, B. Abram, J. E. Taylor, J. Upton, C. F. Tay, S. Fiedler, S. Pullen, L. P. Miller, et al. Thermotolerant Guard Cell Protoplasts of Tree Tobacco Do Not Require Exogenous Hormones to Survive in Culture and Are Blocked from Reentering the Cell Cycle at the G1-to-S Transition Plant Physiology, August 1, 2003; 132(4): 1925 - 1940. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Liao, R. Bucala, and R. A. Mitchell Adhesion-dependent Signaling by Macrophage Migration Inhibitory Factor (MIF) J. Biol. Chem., January 3, 2003; 278(1): 76 - 81. [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 |