Translin restricts the growth of pubertal mammary epithelial cells estrogen-independently in mice

Leo Matsubara1, Tomoya Fukuoka1, Katsuko Sudo2

  • 1Laboratory of Hematology, Division of Medical Biophysics, Kobe University Graduate School of Health Sciences, 7-10-2 Tomogaoka, Suma-ku, Kobe, 654-0142, Japan.

Insights

Translin protein restricts the growth of mammary epithelial cells. Loss of Translin leads to enhanced cell growth and DNA synthesis, particularly after puberty, indicating its role beyond mesenchymal cells.

Area of Science:

  • Cell Biology
  • Developmental Biology
  • Molecular Biology

Background:

  • Translin, an RNA/DNA-binding protein, restricts mesenchymal precursor cell growth and differentiation.
  • The role of Translin in epithelial cells, specifically mammary epithelial cells, is not well understood.

Purpose of the Study:

  • To investigate the role of Translin in the growth and development of pubertal mammary epithelial cells.
  • To determine if Translin influences mammary gland growth independently of hormonal ligands.

Main Methods:

  • Analysis of mammary gland development in Translin-null mice before and after puberty.
  • Primary cell culture of Translin-null mammary epithelial cells to assess DNA synthesis.
  • Hormone pellet implantation studies in ovariectomized Translin-null mice.
  • Luciferase reporter assays to evaluate estrogen receptor α function.

Main Results:

  • Translin-null females showed retarded mammary epithelial growth before puberty but enhanced growth and DNA synthesis post-puberty.
  • Primary Translin-null mammary epithelial cells exhibited augmented DNA synthesis, both ligand-independent and ligand-enhanced.
  • Estrogen treatment in Translin-null mice led to increased mammary gland length and branching.
  • Mammary epithelial growth occurred even without estrogen, suggesting an intrinsic growth restriction role for Translin.

Conclusions:

  • Translin plays a crucial role in restricting the intrinsic growth of pubertal mammary epithelial cells.
  • This function extends beyond its previously known role in mesenchymal precursor cells.
  • Translin's regulation of mammary epithelial cell proliferation is significant for normal development.