help button home button Endocrine Society Molecular Endocrinology ENDO 08 Sessions Library
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Molecular Endocrinology Vol. 5, No. 12 1983-1992
doi:10.1210/mend-5-12-1983
Copyright © 1991 by the Endocrine Society.
This Article
Right arrow Full Text (PDF)
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 Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Tzukerman, M.
Right arrow Articles by Pfahl, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tzukerman, M.
Right arrow Articles by Pfahl, M.

Inhibition of Estrogen Receptor Activity by the Tumor Promoter 12-O-Tetradeconylphorbol-13-Acetate: A Molecular Analysis

Maty Tzukerman, Xiao-Kun Zhang* and Magnus Pfahl

La Jolla Cancer Research Foundation La Jolla, California 92037

Address requests for reprints to: Dr. Magnus Pfahl, La Jolla Cancer Research Foundation, 10901 N. Torrey Pines Road, La Jolla, California 92037.

Abstract

Cell proliferation and phenotype of cells from female reproductive tissues are regulated by estrogens. It is therefore important to understand how estrogen action can be modulated. It recently has been reported that certain nuclear receptors can antagonize the tumor promoter 12-O-tetradeconyIphorbol-13-acetate (TPA) by direct interaction with the transcription factor AP-1, and that the AP-1 constituents cJun and cFos can inhibit receptor activity. This mutual antagonism appears to be based on direct proteinprotein interaction. In the human breast cancer cell line MCF-7, TPA leads to growth arrest and altered cell morphology. We have investigated here whether in MCF-7 cells and other cell lines AP-1 and estrogen receptors (ERs) can inhibit each other's activity. We find that TPA or the AP-1 components cJun and cFos can inhibit estradioldependent estrogen receptor activity in most cell lines investigated. In addition, ER mRNA is rapidly down-regulated in MCF-7 cells. Gel retardation experiments show that ER DNA bind-ing is inhibited in vitro by cJun protein, while ER also can inhibit cJun DNA binding. However, in vivo we do not observe inhibition of AP-1 activity by ER in the cell lines investigated here. On the contrary, we observed an enhancing effect at low ER concentra-tions on AP-1. Together our data suggest a new regulatory pathway by which ER activity can be modulated by AP-1. Several mechanisms including ER-AP-1 protein interaction appear to be involved.

FOOTNOTES

This work was supported by NIH Grant DK-35083 and a grant from the Tobacco-Related Disease Program of the University of California (2RT0109).

* Supported by a postdoctoral fellowship from the Tobacco-Related Disease Research Program of the University of Cali-fornia

Received for publication August 26, 1991. Revision received October 1, 1991. Accepted for publication October 7, 1991.




This article has been cited by other articles:


Home page
 J Mol EndocrinolHome page
S. Safe and K. Kim
Non-classical genomic estrogen receptor (ER)/specificity protein and ER/activating protein-1 signaling pathways
J. Mol. Endocrinol., November 1, 2008; 41(5): 263 - 275.
[Abstract] [Full Text] [PDF]

Home page
 Ann Rheum DisHome page
P. Richette, M.-F. Dumontier, K. Tahiri, M. Widerak, A. Torre, M. Benallaloua, F. Rannou, M.-T. Corvol, and J.-F. Savouret
Oestrogens inhibit interleukin 1{beta}-mediated nitric oxide synthase expression in articular chondrocytes through nuclear factor-{kappa}B impairment
Ann Rheum Dis, March 1, 2007; 66(3): 345 - 350.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
A. Vivacqua, D. Bonofiglio, A. G. Recchia, A. M. Musti, D. Picard, S. Ando, and M. Maggiolini
The G Protein-Coupled Receptor GPR30 Mediates the Proliferative Effects Induced by 17{beta}-Estradiol and Hydroxytamoxifen in Endometrial Cancer Cells
Mol. Endocrinol., March 1, 2006; 20(3): 631 - 646.
[Abstract] [Full Text] [PDF]

Home page
 Endocr Relat CancerHome page
R I Nicholson, I R Hutcheson, S E Hiscox, J M Knowlden, M Giles, D Barrow, and J M W Gee
Growth factor signalling and resistance to selective oestrogen receptor modulators and pure anti-oestrogens: the use of anti-growth factor therapies to treat or delay endocrine resistance in breast cancer
Endocr. Relat. Cancer, July 1, 2005; 12(Supplement_1): S29 - S36.
[Abstract] [Full Text] [PDF]

Home page
 Endocr Relat CancerHome page
R I Nicholson, C Staka, F Boyns, I R Hutcheson, and J M W Gee
Growth factor-driven mechanisms associated with resistance to estrogen deprivation in breast cancer: new opportunities for therapy
Endocr. Relat. Cancer, December 1, 2004; 11(4): 623 - 641.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
S. Chu, Y. Nishi, T. Yanase, H. Nawata, and P. J. Fuller
Transrepression of Estrogen Receptor {beta} Signaling by Nuclear Factor-{kappa}B in Ovarian Granulosa Cells
Mol. Endocrinol., August 1, 2004; 18(8): 1919 - 1928.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. Maggiolini, A. Vivacqua, G. Fasanella, A. G. Recchia, D. Sisci, V. Pezzi, D. Montanaro, A. M. Musti, D. Picard, and S. Ando
The G Protein-coupled Receptor GPR30 Mediates c-fos Up-regulation by 17{beta}-Estradiol and Phytoestrogens in Breast Cancer Cells
J. Biol. Chem., June 25, 2004; 279(26): 27008 - 27016.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
J. N. Holloway, S. Murthy, and D. El-Ashry
A Cytoplasmic Substrate of Mitogen-Activated Protein Kinase Is Responsible for Estrogen Receptor-{alpha} Down-Regulation in Breast Cancer Cells: The Role of Nuclear Factor-{kappa}B
Mol. Endocrinol., June 1, 2004; 18(6): 1396 - 1410.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
H. E. Cunliffe, M. Ringner, S. Bilke, R. L. Walker, J. M. Cheung, Y. Chen, and P. S. Meltzer
The Gene Expression Response of Breast Cancer to Growth Regulators: Patterns and Correlation with Tumor Expression Profiles
Cancer Res., November 1, 2003; 63(21): 7158 - 7166.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
F. Aslam, L. McCabe, B. Frenkel, A. J. van Wijnen, G. S. Stein, J. B. Lian, and J. L. Stein
AP-1 and Vitamin D Receptor (VDR) Signaling Pathways Converge at the Rat Osteocalcin VDR Element: Requirement for the Internal Activating Protein-1 Site for Vitamin D-Mediated Trans-Activation
Endocrinology, January 1, 1999; 140(1): 63 - 70.
[Abstract] [Full Text]

Home page
 EndocrinologyHome page
S. Migliaccio, T. F. Washburn, S. Fillo, H. Rivera, A. Teti, K. S. Korach, and W. C. Wetsel
Modulation of Estrogen Receptor Levels in Mouse Uterus by Protein Kinase C Isoenzymes
Endocrinology, November 1, 1998; 139(11): 4598 - 4606.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
R. Duan, W. Porter, and S. Safe
Estrogen-Induced c-fos Protooncogene Expression in MCF-7 Human Breast Cancer Cells: Role of Estrogen Receptor Sp1 Complex Formation
Endocrinology, April 1, 1998; 139(4): 1981 - 1990.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
N. Sato, M. D. Sadar, N. Bruchovsky, F. Saatcioglu, P. S. Rennie, S. Sato, P. H. Lange, and M. E. Gleave
Androgenic Induction of Prostate-specific Antigen Gene Is Repressed by Protein-Protein Interaction between the Androgen Receptor and AP-1/c-Jun in the Human Prostate Cancer Cell Line LNCaP
J. Biol. Chem., July 11, 1997; 272(28): 17485 - 17494.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M.-O. Lee, M. I. Dawson, N. Picard, P. D. Hobbs, and M. Pfahl
A Novel Class of Retinoid Antagonists and Their Mechanism of Action
J. Biol. Chem., May 17, 1996; 271(20): 11897 - 11903.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
E. Kalkhoven, S. Wissink, P. T. van der Saag, and B. van der Burg
Negative Interaction between the RelA(p65) Subunit of NF-kappaB and the Progesterone Receptor
J. Biol. Chem., March 15, 1996; 271(11): 6217 - 6224.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. B. Martin, P. Garcia-Morales, A. Stoica, H. B. Solomon, M. Pierce, D. Katz, S. Zhang, M. Danielsen, and M. Saceda
Effects of 12-O-Tetradecanoylphorbol-13-acetate on Estrogen Receptor Activity in MCF-7 Cells
J. Biol. Chem., October 20, 1995; 270(42): 25244 - 25251.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
J. Frangioni, N Moghal, A Stuart-Tilley, B. Neel, and S. Alper
The DNA binding domain of retinoic acid receptor beta is required for ligand-dependent suppression of proliferation. Application of general purpose mammalian coexpression vectors
J. Cell Sci., January 4, 1994; 107(4): 827 - 838.
[Abstract] [PDF]

Home page
 J. Biol. Chem.Home page
B. Saville, H. Poukka, M. Wormke, O. A. Janne, J. J. Palvimo, M. Stoner, I. Samudio, and S. Safe
Cooperative Coactivation of Estrogen Receptor alpha in ZR-75 Human Breast Cancer Cells by SNURF and TATA-binding Protein
J. Biol. Chem., January 18, 2002; 277(4): 2485 - 2497.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 1991 by The Endocrine Society