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Atbf1 regulates pubertal mammary gland development likely by inhibiting the pro-proliferative function of estrogen-ER

Mei Li1, Xiaoying Fu, Gui Ma

  • 1Department of Genetics and Cell Biology, College of Life Sciences, Nankai University, Tianjin, China.

Plos One
|December 20, 2012
PubMed

Insights

ATBF1, a tumor suppressor, regulates mammary gland development by interacting with estrogen receptors (ER). Its absence promotes cell proliferation and ductal growth during puberty.

Area of Science:

  • Endocrinology
  • Developmental Biology
  • Cancer Biology

Background:

  • ATBF1 acts as a tumor suppressor, inhibiting estrogen receptor (ER) signaling in breast cancer.
  • Estrogen is crucial for pubertal mammary gland development.

Purpose of the Study:

  • To investigate the role of Atbf1 and its interaction with ER in pubertal mammary gland development.
  • To determine how Atbf1 influences mammary gland morphogenesis and cell proliferation.

Main Methods:

  • In vitro studies using MCF10A cells cultured in Matrigel.
  • In vivo studies involving Atbf1 knockout mice during pubertal mammary gland development.
  • Analysis of ductal elongation, bifurcation, cell proliferation, and marker gene expression (ER, CK5, CK14, CD44).

Main Results:

  • ATBF1 expression increased during in vitro differentiation, and its knockdown inhibited acinus formation.
  • Atbf1 expression varied during mouse mammary gland development, peaking during lactation.
  • Atbf1 knockout enhanced pubertal mammary gland ductal elongation, bifurcation, and ER-positive cell proliferation.
  • Atbf1 inactivation reduced basal cell markers but not luminal cell markers.

Conclusions:

  • Atbf1 is essential for normal pubertal mammary gland development.
  • Atbf1 likely modulates estrogen-ER signaling in luminal cells and affects gene expression in basal cells.
  • These findings highlight Atbf1's role in mammary gland morphogenesis and its potential as a tumor suppressor through ER pathway regulation.

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