| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Department of Molecular and Cellular Biology and The Breast Center (A.J.M., R.E.H., C.K.O.) and Department of Medicine and The Breast Center (R.S., C.K.O.), Baylor College of Medicine, Houston, Texas 77030; and Department of Medicine (E.C.H.), University of Texas Health Science Center at San Antonio, San Antonio, Texas 78284
Address all correspondence and requests for reprints to: C. Kent Osborne, M.D., Baylor College of Medicine, The Breast Center, One Baylor Plaza, MS 600, Houston, Texas 77030. E-mail: kosborne{at}breastcenter.tmc.edu.
Repression of the transcriptional activities of the estrogen receptor (ER) is a main goal in the treatment of breast cancer. The antiestrogen tamoxifen is an effective therapy for breast cancer patients because it inhibits estrogen-stimulated gene expression and cell proliferation. Previous studies have implicated a complex containing the nuclear receptor corepressor (N-CoR) in the mechanism by which tamoxifen represses ER-mediated transcriptional activity. In the present study a truncated N-CoR construct was used to inhibit endogenous N-CoR activity in an ER-positive breast cancer cell line. This dominant-negative N-CoR was successful in relieving repression conferred by the unliganded retinoic acid receptor, but it failed to affect the transcriptional activity of the ER in the presence of tamoxifen. Correspondingly, the histone acetylation levels of nucleosomes on endogenous estrogen-responsive genes were unaltered in cells expressing the N-CoR dominant-negative, regardless of ligand. In addition, in vitro cell proliferation and in vivo tumor growth were unchanged in cells that express dominant-negative N-CoR. In conclusion, these results may reveal that N-CoR affects tamoxifen-liganded ER in a manner distinct from its influence on retinoic acid receptor-mediated transcriptional activity or that corepressors other than N-CoR may be involved in the ability of tamoxifen to repress estrogen-responsive transcription and tumor growth.
NURSA Molecule Pages Link:
This article has been cited by other articles:
 |
|
 |
|
  S. Karmakar, E. A. Foster, and C. L. Smith Unique Roles of p160 Coactivators for Regulation of Breast Cancer Cell Proliferation and Estrogen Receptor-{alpha} Transcriptional Activity Endocrinology, April 1, 2009; 150(4): 1588 - 1596. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. J. Higgins, S. Liu, M. Abdelrahim, K. Vanderlaag, X. Liu, W. Porter, R. Metz, and S. Safe Vascular Endothelial Growth Factor Receptor-2 Expression Is Down-Regulated by 17{beta}-Estradiol in MCF-7 Breast Cancer Cells by Estrogen Receptor {alpha}/Sp Proteins Mol. Endocrinol., February 1, 2008; 22(2): 388 - 402. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. J. Peterson, S. Karmakar, M. C. Pace, T. Gao, and C. L. Smith The Silencing Mediator of Retinoic Acid and Thyroid Hormone Receptor (SMRT) Corepressor Is Required for Full Estrogen Receptor {alpha} Transcriptional Activity Mol. Cell. Biol., September 1, 2007; 27(17): 5933 - 5948. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. K. Keeton and M. Brown Cell Cycle Progression Stimulated by Tamoxifen-Bound Estrogen Receptor-{alpha} and Promoter-Specific Effects in Breast Cancer Cells Deficient in N-CoR and SMRT Mol. Endocrinol., June 1, 2005; 19(6): 1543 - 1554. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Zhou, M. M. Tabb, A. Sadatrafiei, F. Grun, and B. Blumberg TOCOTRIENOLS ACTIVATE THE STEROID AND XENOBIOTIC RECEPTOR, SXR, AND SELECTIVELY REGULATE EXPRESSION OF ITS TARGET GENES Drug Metab. Dispos., October 1, 2004; 32(10): 1075 - 1082. [Abstract] [Full Text] [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 |
