EM-800, a novel antiestrogen, acts as a pure antagonist of the transcriptional functions of estrogen receptors alpha and beta

Endocrinology
A TremblayV Giguère

Abstract

Estrogens act as potent mitogens in a large number of breast cancers, and the use of estrogen receptor (ER) antagonists is, therefore, considered the endocrine therapy of choice in the management of this disease. We describe the molecular properties of EM-652, the active metabolite of EM-800, a novel nonsteroidal antiestrogen compound, on the transcriptional functions of ER alpha and ER beta. Using RT-PCR, we show that ER alpha and ER beta are expressed in mouse mammary glands, suggesting that both receptors should be considered putative targets for antiestrogen action in the breast. In cotransfection assays using a synthetic estrogen-responsive promoter, EM-652 shows no agonistic activity on ER alpha and ER beta transcriptional function and blocks the estradiol (E2)-mediated activation of both ER alpha and ER beta. EM-652 is also very effective in abrogating E2-stimulated ER alpha and ER beta trans-activation of the pS2 promoter in HeLa cells. EM-652 does not alter binding of ER alpha and ER beta to DNA. The Ras-mediated induction of ER alpha and ER beta transcriptional activity in the presence of E2 is also completely abolished by EM-652. In addition, EM-652 blocks the E2-dependent activation of ER alpha and ER beta by the st...Continue Reading

References

Sep 1, 1992·The Journal of Steroid Biochemistry and Molecular Biology·A E Wakeling, J Bowler
Jul 1, 1992·The Journal of Steroid Biochemistry and Molecular Biology·S Z Haslam, K A Nummy
Oct 1, 1987·Molecular Endocrinology·R WhiteM Parker
Feb 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·M BerryP Chambon
Jan 1, 1989·Molecular and Cellular Biology·L Klein-HitpassB W O'Malley
Dec 24, 1987·Cell·V KumarP Chambon
Jan 1, 1984·Pharmacology & Therapeutics·B J Furr, V C Jordan
Jan 1, 1980·Anatomy and Embryology·R NarbaitzM Sar
Jun 12, 1995·Annals of the New York Academy of Sciences·R I NicholsonB S Katzenellenbogen
Jan 1, 1993·Breast Cancer Research and Treatment·A E Wakeling
Jun 11, 1996·Proceedings of the National Academy of Sciences of the United States of America·G G KuiperJ A Gustafsson
Sep 17, 1996·Proceedings of the National Academy of Sciences of the United States of America·E M McInerneyB S Katzenellenbogen

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Citations

Feb 3, 2000·Proceedings of the National Academy of Sciences of the United States of America·M SchapiraR Abagyan
Oct 13, 2001·Trends in Cardiovascular Medicine·Z BianJ A Gustafsson
May 19, 2001·The Journal of Steroid Biochemistry and Molecular Biology·A Tremblay, V Giguère
Feb 19, 2002·The Journal of Steroid Biochemistry and Molecular Biology·F LabrieG Tremblay
Jul 27, 1999·The Journal of Steroid Biochemistry and Molecular Biology·F LabrieR Veilleux
Oct 20, 2009·Trends in Endocrinology and Metabolism : TEM·Mélanie SanchezAndré Tremblay
Jan 7, 2004·British Journal of Pharmacology·Kenichi SakuraiChisato Mori
Nov 4, 1998·Frontiers in Neuroendocrinology·G G KuiperJ A Gustafsson
Mar 3, 2004·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Fernand LabrieBernard Candas
Apr 18, 2003·Biology of Reproduction·Karen D CarpenterThomas E Spencer
Aug 22, 2001·Biology of Reproduction·C A OliveiraR A Hess
May 20, 2000·Bioorganic & Medicinal Chemistry·S H Kim, J A Katzenellenbogen
Mar 12, 2003·Bioorganic & Medicinal Chemistry·Jonathan M SchmidtPeter R Redden
Feb 20, 2007·Archives of Biochemistry and Biophysics·Jeongeun Lee, Stephen Safe
Sep 18, 1999·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·N ZepsH J Dawkins
Nov 19, 2003·Breast Cancer Research and Treatment·Jenny RoyFernand Labrie
Aug 5, 2000·International Journal of Obesity and Related Metabolic Disorders : Journal of the International Association for the Study of Obesity·F PicardD Richard
Dec 24, 2005·Shock·Mashkoor A ChoudhryIrshad H Chaudry
Nov 14, 1998·The Journal of Clinical Endocrinology and Metabolism·T OrdögE Knobil
Aug 5, 2000·Endocrinology·W P BocchinfusoK S Korach
Mar 10, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Carol J Fabian, Bruce F Kimler
May 30, 2013·Expert Opinion on Therapeutic Patents·Ilaria PaterniFilippo Minutolo
Apr 12, 2000·Cancer Control : Journal of the Moffitt Cancer Center·S E Minton
Oct 16, 2015·Journal of Gynecologic Oncology·Vishal ChandraRajani Rai
Apr 4, 2003·Journal of Medicinal Chemistry·Jonathan M SchmidtPeter R Redden
May 31, 2002·Journal of Medicinal Chemistry·Bradley P MorganJon Bordner

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