Atbf1 regulates pubertal mammary gland development likely by inhibiting the pro-proliferative function of estrogen-ER signaling.
Atbf1 regulates pubertal mammary gland development likely by inhibiting the pro-proliferative function of estrogen-ER signaling.
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DOI：
10.1371/journal.pone.0051283
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Dong JT
中科院分区：
文献类型：
--
作者：
Li M;Fu X;Ma G;Sun X;Dong X;Nagy T;Xing C;Li J;Dong JT
ATBF 1是一种候选肿瘤抑制因子，与雌激素受体（ER）相互作用，抑制雌激素-ER信号在人乳腺癌细胞基因调控和细胞增殖控制中的功能。因此，我们测试是否Atbf 1及其与ER的相互作用调节青春期乳腺的发育，其中雌激素是主要的类固醇激素。在细胞分化的体外模型中，即，在Matrigel中培养的MCF 10A细胞中，ATBF 1的表达显著增加，并且ATBF 1的敲低抑制腺泡的形成。在小鼠乳腺发育过程中，Atbf 1在不同阶段表达水平不同，青春期表达水平较高，妊娠期表达水平较低，哺乳期表达水平最高。在青春期开始时敲除Atbf 1增强了导管的伸长和分叉，并促进了青春期乳腺导管和末端芽中的细胞增殖。增强的细胞增殖主要发生在ER阳性细胞中，并伴随着ER靶基因表达的增加。此外，Atbf 1的失活降低了基底细胞标志物（CK 5、CK 14和CD 44）的表达，但不降低管腔细胞标志物的表达。这些发现表明，Atbf 1在青春期乳腺的发育中发挥作用，可能通过调节腔细胞中的雌激素-ER信号传导的功能和通过调节基底细胞中的基因表达。
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.
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DOI：
10.1042/bj20111890
发表时间：
2012-06-15
期刊：
The Biochemical journal
影响因子：
--
作者：
Dong XY;Fu X;Fan S;Guo P;Su D;Dong JT
通讯作者：
Dong JT
影响因子：
3.8
作者：
Cleton-Jansen, Anne-Marie;van Eijk, Ronald;Lombaerts, Marcel;Schmidt, Marjanka K.;Van't Veer, Laura J.;Philippo, Katja;Zimmerman, Rhyenne M. E.;Peterse, Johannes L.;Smit, Vincent T. B. H. M.;van Wezel, Tom;Cornelisse, Cees J.
通讯作者：
Cornelisse, Cees J.
影响因子：
3.8
作者：
Kai K;Zhang Z;Yamashita H;Yamamoto Y;Miura Y;Iwase H
通讯作者：
Iwase H
影响因子：
7.3
作者：
Jones, JL;Shaw, JA;Walker, RA
通讯作者：
Walker, RA
影响因子：
4.8
作者：
Debnath, J;Muthuswamy, SK;Brugge, JS
通讯作者：
Brugge, JS