Transforming growth factor-beta1 mediates cellular response to DNA damage in situ

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Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage
10:59

Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage

Published on: August 21, 2021

Kenneth B Ewan1, Rhonda L Henshall-Powell, Shraddha A Ravani

  • 1Lawrence Berkeley National Laboratory, University of California, Berkeley 94720, USA.

Cancer Research
|October 18, 2002
PubMed

Insights

Transforming growth factor-beta1 (TGF-beta1) is crucial for the DNA damage response. This study shows TGF-beta1 is essential for radiation-induced apoptosis and p53 activation in mammary cells.

Area of Science:

  • Cellular and Molecular Biology
  • Radiation Oncology
  • Cancer Research

Background:

  • Ionizing radiation triggers rapid activation of transforming growth factor-beta1 (TGF-beta1).
  • The precise role of TGF-beta1 in cellular responses to DNA damage remains unclear.
  • TGF-beta1 signaling is implicated in various cellular processes, including apoptosis and proliferation.

Purpose of the Study:

  • To elucidate the role of TGF-beta1 in radiation-induced cellular responses, specifically apoptosis and proliferation inhibition.
  • To investigate the dependence of p53 activation on TGF-beta1 following DNA damage.
  • To determine the impact of TGF-beta1 gene dose on cellular responses in embryonic epithelial tissues.

Main Methods:

  • Utilized Tgfbeta1 knockout mice to assess the impact of TGF-beta1 deficiency on radiation responses.
  • Examined apoptosis and proliferation inhibition in mammary epithelium and embryonic epithelial tissues after irradiation.
  • Assessed p53 protein activation, specifically Ser-18 phosphorylation, in irradiated mammary glands under conditions of TGF-beta1 depletion.

Main Results:

  • Radiation-induced apoptosis in the mammary epithelium is dependent on TGF-beta1.
  • Both apoptosis and proliferation inhibition in response to DNA damage decrease with decreasing TGF-beta1 gene dose in embryonic epithelial tissues.
  • TGF-beta1 depletion (via gene knockout or neutralizing antibodies) led to reduced p53 Ser-18 phosphorylation in irradiated mammary glands.

Conclusions:

  • TGF-beta1 is essential for the rapid, p53-mediated cellular responses to DNA damage.
  • TGF-beta1 plays a critical role in mediating cell fate decisions in situ following radiation exposure.
  • The findings highlight TGF-beta1 as a key regulator of DNA damage response pathways.
Keywords:
NASA Discipline Radiation HealthNon-NASA Center

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