Atbf1 Regulates Pubertal Mammary Gland Development Likely by Inhibiting the Pro-Proliferative Function of Estrogen-ER Signaling

• Type of Material: Article
• Authors: Mei Li, Emory University; Xiaoying Fu, Emory University; Gui Ma, Nankai University; Xiaodong Sun, Emory University; Xueyuan Dong, Emory University; Tamas Nagy, University of Georgia; Changsheng Xing, Emory University; Jie Li, Emory University; Jin-Tang Dong, Emory University
• Language: English
• Date: 2012-12-12
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: © 2012 Li et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0051283
• Title of Journal or Parent Work: PLoS ONE
• ISSN: 1932-6203
• Volume: 7
• Issue: 12
• Start Page: 1
• End Page: 12
• Grant/Funding Information: This work was supported by NIH grant CA121459.
• Research Categories: Health Sciences, Pathology; Health Sciences, Oncology; Biology, Genetics; Biology, Cell

Abstract

ATBF1 is a candidate tumor suppressor that interacts with estrogen receptor (ER) to inhibit the function of estrogen-ER signaling in gene regulation and cell proliferation control in human breast cancer cells. We therefore tested whether Atbf1 and its interaction with ER modulate the development of pubertal mammary gland, where estrogen is the predominant steroid hormone. In an in vitro model of cell differentiation, i.e., MCF10A cells cultured in Matrigel, ATBF1 expression was significantly increased, and knockdown of ATBF1 inhibited acinus formation. During mouse mammary gland development, Atbf1 was expressed at varying levels at different stages, with higher levels during puberty, lower during pregnancy, and the highest during lactation. Knockout of Atbf1 at the onset of puberty enhanced ductal elongation and bifurcation and promoted cell proliferation in both ducts and terminal end buds of pubertal mammary glands. Enhanced cell proliferation primarily occurred in ER-positive cells and was accompanied by increased expression of ER target genes. Furthermore, inactivation of Atbf1 reduced the expression of basal cell markers (CK5, CK14 and CD44) but not luminal cell markers. These findings indicate that Atbf1 plays a role in the development of pubertal mammary gland likely by modulating the function of estrogen-ER signaling in luminal cells and by modulating gene expression in basal cells.