HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 280, Issue 9, 7829-7835, March 4, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/9/7829    most recent M412707200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by White, K. A. Articles by Spinella, M. J. Search for Related Content PubMed PubMed Citation Articles by White, K. A. Articles by Spinella, M. J. Social Bookmarking                      What's this?

Limiting Effects of RIP140 in Estrogen Signaling

POTENTIAL MEDIATION OF ANTI-ESTROGENIC EFFECTS OF RETINOIC ACID^*

Kristina A. White, Mark M. Yore, Dexin Deng, and Michael J. Spinella

From the Department of Pharmacology and Toxicology, Dartmouth Medical School, and the Norris Cotton Cancer Center, Dartmouth Hitchcock Medical Center, Hanover, New Hampshire 03755

The receptor interacting protein 140 (RIP140) belongs to a unique subclass of nuclear receptor coregulators with the ability to bind and repress the action of a number of agonist-bound hormone receptors. We have previously demonstrated that all-trans-retinoic acid (RA) induction of RIP140 constitutes a rate-limiting step in the regulation of retinoid receptor signaling. Here we demonstrate that RIP140 is also a limiting regulator of estrogen receptor signaling. Overexpression of RIP140 dose dependently inhibits estrogen-dependent reporter activity in human breast cancer cells. Furthermore, small interfering RNA to RIP140 enhances estrogen-dependent signaling. Our previous studies indicate that RIP140 is a direct target of RA. We report here that RA can abrogate estrogen-mediated cell cycle re-entry. In addition, RA treatment of estrogen-dependent breast cancer cells opposes estrogen receptor-dependent reporter activity, implying that a proportion of RA effects are anti-estrogenic. We provide evidence for a role for RIP140 in mediating anti-estrogenic effects of RA. RIP140 small interfering RNA blocks RA-mediated repression of estrogen receptor activity and provides a growth advantage to estrogen-dependent cells. Together these data implicate a regulatory role for RIP140 in mediating anti-estrogenic effects of RA in estrogendependent breast cancer cells and suggest that acute regulation of coregulator expression may be a general mechanism to integrate diverse hormone signals.

Received for publication, November 10, 2004 , and in revised form, December 21, 2004.

^* This work was supported in part by National Institutes of Health Grant R01-CA104312 (to M. J. S.) and American Cancer Society Grant RSG-01-144-01 (to M. J. S.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Recipient of Pre-graduate Fellowship BC010159 from the Department of Defense.

To whom correspondence should be addressed: Dept. of Pharmacology and Toxicology, Dartmouth Medical School, 7650 Remsen, Hanover, NH 03755. Tel.: 603-650-1920; Fax: 603-650-1129; E-mail: michael.spinella{at}dartmouth.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				B. B. Cheung, J. Bell, A. Raif, A. Bohlken, J. Yan, B. Roediger, A. Poljak, S. Smith, M. Lee, W. D. Thomas, et al. The Estrogen-responsive B Box Protein Is a Novel Regulator of the Retinoid Signal J. Biol. Chem., June 30, 2006; 281(26): 18246 - 18256. [Abstract] [Full Text] [PDF]

				J. Laganiere, G. Deblois, and V. Giguere Functional Genomics Identifies a Mechanism for Estrogen Activation of the Retinoic Acid Receptor {alpha}1 Gene in Breast Cancer Cells Mol. Endocrinol., June 1, 2005; 19(6): 1584 - 1592. [Abstract] [Full Text] [PDF]