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The Ras-like protein R-Ras2/TC21 is important for proper mammary gland development

Romain M Larive1, Antonio Abad, Clara M Cardaba

  • 1Centro de Investigación del Cáncer, Consejo Superior de Investigaciones Científicas-University of Salamanca, E37007 Salamanca, Spain.

Molecular Biology of the Cell
|April 27, 2012
PubMed

Insights

The GTPase R-Ras2/TC21 is crucial for mammary gland development in mice. Its absence leads to reduced branching and proliferation in epithelial cells during puberty.

Area of Science:

  • Molecular Biology
  • Developmental Biology
  • Cell Signaling

Background:

  • R-Ras2/TC21 is a GTPase with similarities to Ras subfamily members.
  • Its physiological role is poorly understood despite extensive cell line studies.

Purpose of the Study:

  • To investigate the in vivo function of R-Ras2/TC21 using knockout mice.
  • To characterize the physiological role of R-Ras2/TC21 in mammalian development.

Main Methods:

  • Generation and analysis of RRas2-knockout mice.
  • Assessment of viability, growth, cardiovascular parameters, fertility, and mammary gland development.
  • Analysis of epithelial cell proliferation and signaling pathways (Erk, Akt).
  • Generation of compound knockout mice (RRas2, HRas, NRas).

Main Results:

  • RRas2(-/-) mice show normal viability, growth, cardiovascular function, and fertility.
  • A specific defect in mammary gland development during puberty was observed in RRas2(-/-) mice.
  • Reduced terminal end buds (TEBs) and ductal branching, with delayed gland tree extension and arborization.
  • Cell-autonomous proliferative defects in TEB epithelial cells, with reduced Erk activation but normal Akt phosphorylation.
  • Ras subfamily GTPases (RRas2, HRas, NRas) act non-synergistically and non-additively in mammary gland morphogenesis.

Conclusions:

  • R-Ras2/TC21 plays a critical, specific role in mammary gland development during puberty.
  • The GTPase is essential for epithelial cell proliferation and Erk signaling in TEBs.
  • R-Ras2/TC21 functions independently of HRas and NRas in this developmental process.

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