Molecular Endocrinology, Vol 5, 1983-1992, Copyright © 1991 by Endocrine Society

ARTICLES

Inhibition of estrogen receptor activity by the tumor promoter 12-O- tetradeconylphorbol-13-acetate: a molecular analysis

M Tzukerman, XK Zhang and M Pfahl
La Jolla Cancer Research Foundation, California 92037.

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-tetradeconylphorbol-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 protein-protein 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 estradiol-dependent 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 binding 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 concentrations 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.

This article has been cited by other articles:

				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]

				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]

				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]

				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]

				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]

				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]

				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]

				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]

				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]

				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]

				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]

				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]

				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]

				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]

				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]

				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]

				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]