help button home button Endocrine Society Molecular Endocrinology ENDO 08 Sessions Library
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
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
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 Santagati, S.
Right arrow Articles by Maggi, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Santagati, S.
Right arrow Articles by Maggi, A.
Molecular Endocrinology 11 (7): 938-949
Copyright © 1997 by The Endocrine Society

Oligonucleotide Squelching Reveals the Mechanism of Estrogen Receptor Autologous Down-Regulation

S. Santagati, E. Gianazza, P. Agrati, E. Vegeto, C. Patrone, G. Pollio and A. Maggi

Center Milan Molecular Pharmacology Laboratory and Laboratory for the Study of Arteriosclerosis (E.G.), Institute of Pharmacological Sciences, University of Milan, I-20133 Milan, Italy

Antisense oligos complementary to the 5'-end, but not to the 3'-end, of the estrogen receptor (ER) messenger RNA caused a paradox accumulation of ER protein in MCF-7 cells. The same effect was observed after treatment of the cells with the corresponding sense oligos. The oligos interfering with ER down-regulation were demonstrated to specifically bind the ER with affinities in the nanomolar range. It is, therefore, proposed that the ER up-regulation induced by the oligos might be due to squelching of the ER (or ER-inducible proteins) from their binding site located in the 5'-end of the ER gene. We also report that transcriptionally inactive ER mutants can undergo down-regulation, and that in denaturing gels, the migration profile of ER-oligo and ER-estrogen-responsive element complexes are dissimilar. We, therefore, propose that ER can interact with DNA in different ways and at different binding sites. These observations might have important pharmacological consequences, since specific drugs could be devised to induce the ER conformation necessary to perform only selected tasks of the ER transcriptional repertoire.




This article has been cited by other articles:


Home page
 Hum ReprodHome page
X. Di, L. Yu, A.B. Moore, L. Castro, X. Zheng, T. Hermon, and D. Dixon
A low concentration of genistein induces estrogen receptor-alpha and insulin-like growth factor-I receptor interactions and proliferation in uterine leiomyoma cells
Hum. Reprod., August 1, 2008; 23(8): 1873 - 1883.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
L. Albanito, A. Madeo, R. Lappano, A. Vivacqua, V. Rago, A. Carpino, T. I. Oprea, E. R. Prossnitz, A. M. Musti, S. Ando, et al.
G Protein-Coupled Receptor 30 (GPR30) Mediates Gene Expression Changes and Growth Response to 17{beta}-Estradiol and Selective GPR30 Ligand G-1 in Ovarian Cancer Cells
Cancer Res., February 15, 2007; 67(4): 1859 - 1866.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
A. Vivacqua, D. Bonofiglio, L. Albanito, A. Madeo, V. Rago, A. Carpino, A. M. Musti, D. Picard, S. Ando, and M. Maggiolini
17beta-Estradiol, Genistein, and 4-Hydroxytamoxifen Induce the Proliferation of Thyroid Cancer Cells through the G Protein-Coupled Receptor GPR30
Mol. Pharmacol., October 1, 2006; 70(4): 1414 - 1423.
[Abstract] [Full Text] [PDF]

Home page
 HypertensionHome page
M. R. Meyer, E. Haas, and M. Barton
Gender Differences of Cardiovascular Disease: New Perspectives for Estrogen Receptor Signaling
Hypertension, June 1, 2006; 47(6): 1019 - 1026.
[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
 J. Biol. Chem.Home page
S. Catalano, L. Mauro, S. Marsico, C. Giordano, P. Rizza, V. Rago, D. Montanaro, M. Maggiolini, M. L. Panno, and S. Ando
Leptin Induces, via ERK1/ERK2 Signal, Functional Activation of Estrogen Receptor {alpha} in MCF-7 Cells
J. Biol. Chem., May 7, 2004; 279(19): 19908 - 19915.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
F. Barchiesi, E. K. Jackson, B. Imthurn, J. Fingerle, D. G. Gillespie, and R. K. Dubey
Differential Regulation of Estrogen Receptor Subtypes {alpha} and {beta} in Human Aortic Smooth Muscle Cells by Oligonucleotides and Estradiol
J. Clin. Endocrinol. Metab., May 1, 2004; 89(5): 2373 - 2381.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
B. M. Wittmann, N. Wang, and M. M. Montano
Identification of a Novel Inhibitor of Breast Cell Growth That Is Down-Regulated by Estrogens and Decreased in Breast Tumors
Cancer Res., August 15, 2003; 63(16): 5151 - 5158.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
E. T. Alarid, M. T. Preisler-Mashek, and N. M. Solodin
Thyroid Hormone Is an Inhibitor of Estrogen-Induced Degradation of Estrogen Receptor-{alpha} Protein: Estrogen-Dependent Proteolysis Is Not Essential for Receptor Transactivation Function in the Pituitary
Endocrinology, August 1, 2003; 144(8): 3469 - 3476.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
M. Fan, X. Long, J. A. Bailey, C. A. Reed, E. Osborne, E. A. Gize, E. A. Kirk, R. M. Bigsby, and K. P. Nephew
The Activating Enzyme of NEDD8 Inhibits Steroid Receptor Function
Mol. Endocrinol., February 1, 2002; 16(2): 315 - 330.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
M. Maggiolini, D. Bonofiglio, S. Marsico, M. L. Panno, B. Cenni, D. Picard, and S. Ando
Estrogen Receptor alpha Mediates the Proliferative but Not the Cytotoxic Dose-Dependent Effects of Two Major Phytoestrogens on Human Breast Cancer Cells
Mol. Pharmacol., September 1, 2001; 60(3): 595 - 602.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
M. Maggiolini, O. Donze, E. Jeannin, S. Ando, and D. Picard
Adrenal Androgens Stimulate the Proliferation of Breast Cancer Cells as Direct Activators of Estrogen Receptor {{alpha}}
Cancer Res., October 1, 1999; 59(19): 4864 - 4869.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
C. Patrone, S. Andersson, L. Korhonen, and D. Lindholm
Estrogen receptor-dependent regulation of sensory neuron survival in developing dorsal root ganglion
PNAS, September 14, 1999; 96(19): 10905 - 10910.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
E. T. Alarid, N. Bakopoulos, and N. Solodin
Proteasome-Mediated Proteolysis of Estrogen Receptor: A Novel Component in Autologous Down-Regulation
Mol. Endocrinol., September 1, 1999; 13(9): 1522 - 1534.
[Abstract] [Full Text]

Home page
 Mol. Endocrinol.Home page
C. Patrone, E. Gianazza, S. Santagati, P. Agrati, and A. Maggi
Divergent Pathways Regulate Ligand-Independent Activation of ER{alpha} in SK-N-BE Neuroblastoma and COS-1 Renal Carcinoma Cells
Mol. Endocrinol., June 1, 1998; 12(6): 835 - 841.
[Abstract] [Full Text]


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 © 1997 by The Endocrine Society