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. 11 1707-1715
doi:10.1210/mend-5-11-1707
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 Wang, Y.
Right arrow Articles by Miksicek, R. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wang, Y.
Right arrow Articles by Miksicek, R. J.

Identification of a Dominant Negative Form of the Human Estrogen Receptor

Yaolin Wang and Richard J. Miksicek

Department of Pharmacological Sciences, State University of New York Stony Brook, New York 11794–8651

Address requests for reprints to: Dr. Richard J. Miksicek, Department of Pharmacological Sciences, State University of New York, Stony Brook, New York 11794–8651.

Abstract

Experiments were undertaken to characterize mRNAs coding for the estrogen receptor (ER) in the human breast cancer cell line T47D. We report here the isolation of cDNAs corresponding to three isoforms of this receptor in addition to a majority of wild-type clones. Sequence analysis showed that these isoforms are generated through alternative splicing. None of the alternatively spliced isoforms of ER is able to bind to an estrogen-responsive element (ERE) in a gel mobility shift assay in vitro or to activate transcription of a reporter gene containing an ERE in vivo. One isoform, ER{delta}E3, which harbors a deletion of exon 3 encoding the second zinc finger of the DNA-binding domain, inhibits estrogen-dependent transcription activation in a dominant negative fashion when it is cotransfected with the wild-type ER and reporter plasmid. It also inhibits DNA binding of wild-type ER in a gel mobility shift assay in vitro. Since ER{delta}E3 is not able to bind to its response element, the observed inhibitory effect probably occurs through protein-protein interactions. This could involve the formation of a heterodimer between mutant and wild-type receptors, competition for a limiting transcription factor, or both. These results may have implications for understanding the loss of estrogen responsiveness that frequently occurs in breast cancer.

FOOTNOTES

This work was supported by NIH Grant CA-4738402, American Cancer Society Grant CD-479, USPHS Biomedical Research Support Grant S07-RR-0573616, and a New York State Science and Technology Grant (to R.J.M.).

Received for publication July 1, 1991. Revision received August 22, 1991. Accepted for publication August 27, 1991.




This article has been cited by other articles:


Home page
 J EndocrinolHome page
J Varayoud, J G Ramos, L Monje, V Bosquiazzo, M Munoz-de-Toro, and E H Luque
The estrogen receptor {alpha} {Sigma}3 mRNA splicing variant is differentially regulated by estrogen and progesterone in the rat uterus
J. Endocrinol., July 1, 2005; 186(1): 51 - 60.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
M. H. Herynk and S. A. W. Fuqua
Estrogen Receptor Mutations in Human Disease
Endocr. Rev., December 1, 2004; 25(6): 869 - 898.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
J. M. Garcia Pedrero, P. Zuazua, C. Martinez-Campa, P. S. Lazo, and S. Ramos
The Naturally Occurring Variant of Estrogen Receptor (ER) ER{Delta}E7 Suppresses Estrogen-Dependent Transcriptional Activation by Both Wild-Type ER{alpha} and ER{beta}
Endocrinology, July 1, 2003; 144(7): 2967 - 2976.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
L. M. Mangravite, G. Xiao, and K. M. Giacomini
Localization of human equilibrative nucleoside transporters, hENT1 and hENT2, in renal epithelial cells
Am J Physiol Renal Physiol, May 1, 2003; 284(5): F902 - F910.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
V. L. Davis, C.-C. Chan, T. J. Schoen, J. F. Couse, G. J. Chader, and K. S. Korach
An estrogen receptor repressor induces cataract formation in transgenic mice
PNAS, July 9, 2002; 99(14): 9427 - 9432.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
L. P. Stabile, A. L. G. Davis, C. T. Gubish, T. M. Hopkins, J. D. Luketich, N. Christie, S. Finkelstein, and J. M. Siegfried
Human Non-Small Cell Lung Tumors and Cells Derived from Normal Lung Express Both Estrogen Receptor {alpha} and {beta} and Show Biological Responses to Estrogen
Cancer Res., April 1, 2002; 62(7): 2141 - 2150.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
C. Pasqualini, D. Guivarc'h, J.-V. Barnier, B. Guibert, J.-D. Vincent, and P. Vernier
Differential Subcellular Distribution and Transcriptional Activity of {{Sigma}}E3, {{Sigma}}E4, and {{Sigma}}E3-4 Isoforms of the Rat Estrogen Receptor-{{alpha}}
Mol. Endocrinol., June 1, 2001; 15(6): 894 - 908.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
A. Bollig and R. J. Miksicek
An Estrogen Receptor-{alpha} Splicing Variant Mediates Both Positive and Negative Effects on Gene Transcription
Mol. Endocrinol., May 1, 2000; 14(5): 634 - 649.
[Abstract] [Full Text]

Home page
 J. Biol. Chem.Home page
E. M. Resnick, D. A. Schreihofer, A. Periasamy, and M. A. Shupnik
Truncated Estrogen Receptor Product-1 Suppresses Estrogen Receptor Transactivation by Dimerization with Estrogen Receptors alpha and beta
J. Biol. Chem., March 15, 2000; 275(10): 7158 - 7166.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
M. L. O’Brien, K. Park, Y. In, and O.-K. Park-Sarge
Characterization of Estrogen Receptor-{beta} (ER{beta}) Messenger Ribonucleic Acid and Protein Expression in Rat Granulosa Cells
Endocrinology, October 1, 1999; 140(10): 4530 - 4541.
[Abstract] [Full Text]

Home page
 J. Biol. Chem.Home page
R. H. Oakley, C. M. Jewell, M. R. Yudt, D. M. Bofetiado, and J. A. Cidlowski
The Dominant Negative Activity of the Human Glucocorticoid Receptor beta Isoform. SPECIFICITY AND MECHANISMS OF ACTION
J. Biol. Chem., September 24, 1999; 274(39): 27857 - 27866.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
C. Pasqualini, D. Guivarc’h, Y. v. Boxberg, F. Nothias, J.-D. Vincent, and P. Vernier
Stage- and Region-Specific Expression of Estrogen Receptor {alpha} Isoforms during Ontogeny of the Pituitary Gland
Endocrinology, June 1, 1999; 140(6): 2781 - 2789.
[Abstract] [Full Text]

Home page
 CirculationHome page
Y. K. Hodges, J. K. Richer, K. B. Horwitz, and L. D. Horwitz
Variant Estrogen and Progesterone Receptor Messages in Human Vascular Smooth Muscle
Circulation, May 25, 1999; 99(20): 2688 - 2693.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. Kitayama, T. Ikeda, C. Mitsuhata, T. Sato, K. Morita, and T. Dohi
Dominant Negative Isoform of Rat Norepinephrine Transporter Produced by Alternative RNA Splicing
J. Biol. Chem., April 16, 1999; 274(16): 10731 - 10736.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
R. L. Balleine, S. M. N. Hunt, and C. L. Clarke
Coexpression of Alternatively Spliced Estrogen and Progesterone Receptor Transcripts in Human Breast Cancer
J. Clin. Endocrinol. Metab., April 1, 1999; 84(4): 1370 - 1377.
[Abstract] [Full Text]

Home page
 Cancer Res.Home page
E. Leygue, H. Dotzlaw, P. H. Watson, and L. C. Murphy
Expression of Estrogen Receptor {beta}1, {beta}2, and {beta}5 Messenger RNAs in Human Breast Tissue
Cancer Res., March 1, 1999; 59(6): 1175 - 1179.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
M. A. Shupnik, L. K. Pitt, A. Y. Soh, A. Anderson, M. B. Lopes, and E. R. Laws Jr.
Selective Expression of Estrogen Receptor {alpha} and {beta} Isoforms in Human Pituitary Tumors
J. Clin. Endocrinol. Metab., November 1, 1998; 83(11): 3965 - 3972.
[Abstract] [Full Text]

Home page
 J. Clin. Endocrinol. Metab.Home page
E. Geimonen, E. Boylston, A. Royek, and J. Andersen
Elevated Connexin-43 Expression in Term Human Myometrium Correlates with Elevated c-Jun Expression and Is Independent of Myometrial Estrogen Receptors
J. Clin. Endocrinol. Metab., April 1, 1998; 83(4): 1177 - 1185.
[Abstract] [Full Text]

Home page
 Mol. Endocrinol.Home page
S. Petersenn, A. C. Rasch, M. Heyens, and H. M. Schulte
Structure and Regulation of the Human Growth Hormone-Releasing Hormone Receptor Gene
Mol. Endocrinol., February 1, 1998; 12(2): 233 - 247.
[Abstract] [Full Text]

Home page
 Mol. Endocrinol.Home page
I. Erenburg, B. Schachter, R. M. y Lopez, and L. Ossowski
Loss of an Estrogen Receptor Isoform (ER{alpha}{Delta}3) in Breast Cancer and the Consequences of Its Reexpression: Interference with Estrogen-Stimulated Properties of Malignant Transformation
Mol. Endocrinol., December 1, 1997; 11(13): 2004 - 2015.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
S. S. Chaidarun, A. Klibanski, and J. M. Alexander
Tumor-Specific Expression of Alternatively Spliced Estrogen Receptor Messenger Ribonucleic Acid Variants in Human Pituitary Adenomas
J. Clin. Endocrinol. Metab., April 1, 1997; 82(4): 1058 - 1065.
[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
 Reproductive SciencesHome page
J. Andersen, V. M. DyReyes, R. L. Barbieri, D. M. Coachman, and R. J. Miksicek
Leiomyoma Primary Cultures Have Elevated Transcriptional Response to Estrogen Compared With Autologous Myometrial Cultures
Reproductive Sciences, May 1, 1995; 2(3): 542 - 551.
[Abstract] [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