ATBF1 Inhibits Estrogen Receptor (ER) Function by Selectively Competing with AIB1 for Binding to the ER in ER-positive Breast Cancer Cells

• Type of Material: Article
• Authors: Xue-Yuan Dong, Emory University; Xiaodong Sun, Emory University; Peng Guo, Emory University; Qunna Li, Emory University; Masakiyo Sasahara, University of Toyama; Yoko Ishii, University of Toyama; Jin-Tang Dong, Emory University
• Language: English
• Date: 2010-10-22
• Publisher: American Society for Biochemistry and Molecular Biology
• Publication Version: Final Published Version
• Copyright Statement: © 2010 by The American Society for Biochemistry and Molecular Biology, Inc.
• Final Published Version (URL): http://www.jbc.org/content/285/43/32801
• Title of Journal or Parent Work: Journal of Biological Chemistry
• ISSN: 0021-9258
• Volume: 285
• Issue: 43
• Start Page: 32801
• End Page: 32809
• Grant/Funding Information: This work was supported, in whole or in part, by National Institutes of Health Grant CA85560 (to J.-T. D.).; This work was also supported by Department of Defense Grant W81XWH-08-1-0328 (to X.-Y. D.) and by Georgia Cancer Coalition Award GCC130042 (to X.-Y. D.).
• Keywords: Tumor Suppressor; Hormone Receptors; ER Function; Breast Cancer; Receptor Regulation; AIB1; Tumor Promoter; ATBF1
• Research Categories: Health Sciences, Oncology; Health Sciences, Pathology; Chemistry, Biochemistry

Abstract

Loss of the q22 band of chromosome 16 is a frequent genetic event in breast cancer, and the candidate tumor suppressor gene, ATBF1, has been implicated in breast cancer by genomic deletion, transcriptional down-regulation, and association with better prognostic parameters. In addition, estrogen receptor (ER)-positive breast cancer expresses a higher level of ATBF1, suggesting a role of ATBF1 in ER-positive breast cancer. In this study, we examined whether and how ATBF1 affects the ER function in breast cancer cells. We found that ATBF1 inhibited ER-mediated gene transcription, cell growth, and proliferation in ER-positive breast cancer cells. In vitro and in vivo immunoprecipitation experiments revealed that ATBF1 interacted physically with the ER and that multiple domains in both ATBF1 and ER proteins mediated the interaction. Furthermore, we demonstrated that ATBF1 inhibited ER function by selectively competing with the steroid receptor coactivator AIB1 but not GRIP1 or SRC1 for binding to the ER. These findings not only support the concept that ATBF1 plays a tumor-suppressive role in breast cancer, they also provide a mechanism for how ATBF1 functions as a tumor suppressor in breast cancer.