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

J. Biol. Chem., Vol. 280, Issue 52, 43188-43197, December 30, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/52/43188    most recent M506598200v1 Alert me when this article is cited 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 Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Zhang, H. Articles by Ye, Q. Search for Related Content PubMed PubMed Citation Articles by Zhang, H. Articles by Ye, Q. Social Bookmarking                      What's this?

Stimulatory Cross-talk between NFAT3 and Estrogen Receptor in Breast Cancer Cells^*

Hao Zhang1, Xiangyang Xie1, Xudong Zhu, Jianhua Zhu, Chunfang Hao, Qiujun Lu¶, Lihua Ding, Yufei Liu, Lei Zhou, Yaling Liu, Cuifen Huang, Chungen Wen, and Qinong Ye2

From the Department of Molecular Oncology and ^¶Department of Pharmacology and Toxicology, Beijing Institute of Biotechnology, Beijing 100850, China and the Department of Biological Science, University of Nanchang, Nanchang 330047, China

Estrogen receptors (ER and ER) are ligand-regulated transcription factors that play critical roles in the development and progression of breast cancer by regulating target genes involved in cellular proliferation. The transcriptional activity of ER and ER is known to be modulated by cofactor proteins. We used a yeast two-hybrid system and identified NFAT3 as a novel ER-binding protein. NFAT3 interacted with ER and ER both in vitro and in mammalian cells in a ligand-independent fashion. NFAT3 bound specifically to the ER region containing the activation function-1 domain, a ligand-independent transactivation domain. Overexpression of NFAT3 enhanced both ER and ER transcriptional activities in a ligand-independent manner and up-regulated downstream estrogen-responsive genes including pS2 and cathepsin D. Reduction of endogenous NFAT3 with NFAT3 small interfering RNA or overexpression of NFAT3 deletion mutants that lack the ER-binding sites reduced the NFAT3 coactivation of ER and ER. NFAT3 increased binding of ER to the estrogen-responsive element and was recruited to endogenous estrogen-responsive promoters. NFAT3 was expressed differentially in many breast cancer cell lines and overexpressed in a subset of breast cancer patients. Knockdown of endogenous NFAT3 reduced the growth of human breast cancer ZR75-1 cells in a ligand-independent manner. Taken together, these results suggest that NFAT3 may play important roles in ER signaling and represent a novel target for breast cancer therapy.

Received for publication, June 17, 2005 , and in revised form, October 5, 2005.

^* This work was supported by National Natural Science Foundation (30470378, 30530320, 30428012, and 30500191) and an Innovative grant from Scientific Research Foundation for the Returned Overseas Chinese Scholars. 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.

¹ These authors contributed equally to this work.

² To whom correspondence should be addressed: Dept. of Molecular Oncology, Beijing Institute of Biotechnology, 27 Tai-Ping Lu Rd., Beijing 100850, China. Tel.: 8610-6818-0809; Fax: 8610-6824-8045; E-mail: yeqn{at}nic.bmi.ac.cn.

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