Repression of endogenous estrogen receptor activity in MCF-7 human breast cancer cells by dominant negative estrogen receptors

Endocrinology
B A InceB S Katzenellenbogen

Abstract

We have investigated the ability of several transcriptionally inactive estrogen receptor (ER) mutants to block endogenous ER-mediated transcription in MCF-7 human breast cancer cells. In transient transfections of MCF-7 cells, two of the mutants, a frame-shifted ER (S554fs) and a point-mutated ER (L540Q), strongly inhibit the ability of endogenous wild-type ER to activate transcription of estrogen-regulated reporter plasmids. A third mutant, ER1-530, which is missing 65 residues from its carboxy-terminus, is a weaker repressor of estradiol-stimulated transcription. When an estrogen response element (ERE)-thymidine kinase-chloramphenicol acetyltransferase reporter gene is used, S554fs, L540Q, and ER1-530 suppress the transcriptional activity of endogenous MCF-7 ER by 87%, 97%, and 62%, respectively. The magnitude of dominant negative repression is promoter specific; when an ERE-pS2-chloramphenicol acetyltransferase reporter is employed, inhibition of endogenous ER activity by equivalent amounts of S554fs, L540Q, and ER1-530 ranges from 85-97%. Dose-response studies show the S554fs mutant to be the most potent of the three ER mutants as a repressor of estrogen action in these cells. In addition, elevated levels of intracellular c...Continue Reading

Citations

Aug 30, 2011·Proceedings of the National Academy of Sciences of the United States of America·Yukitomo AraoKenneth S Korach
Jun 9, 1999·Proceedings of the National Academy of Sciences of the United States of America·M M MontanoB S Katzenellenbogen
Mar 26, 2008·Endocrine·Debra F Skafar, Changqing Zhao
Dec 13, 2006·International Journal of Hygiene and Environmental Health·William W AuAyman Al-Hendy
May 19, 2009·Advanced Drug Delivery Reviews·Memy H HassanAyman Al-Hendy
Dec 8, 2004·Endocrine Reviews·Matthew H Herynk, Suzanne A W Fuqua
May 30, 2003·Molecular and Cellular Biology·Matthew R YudtJohn A Cidlowski
Apr 25, 2002·Molecular and Cellular Biology·Anne C NyeAndrew S Belmont
Apr 18, 2018·Nature Reviews. Cancer·John A KatzenellenbogenSarat Chandarlapaty
Dec 29, 1995·The Journal of Biological Chemistry·D J SchodinB S Katzenellenbogen
Dec 24, 2002·The Journal of Biological Chemistry·Sandra Timm PearceV Craig Jordan
Jan 1, 1997·American Journal of Obstetrics and Gynecology·L B SchwartzK Mittal

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