Transforming growth factor-β1 mediates cellular response to DNA damage in situ

Kenneth B. Ewan, Rhonda L. Henshall-Powell, Shraddha A. Ravani, Maria Jose Pajares, Carlos Arteaga, Ray Warters, Rosemary J. Akhurst, Mary Helen Barcellos-Hoff

Research output: Contribution to journalArticlepeer-review

130 Scopus citations

Abstract

Transforming growth factor (TGF)-β1 is rapidly activated after ionizing radiation, but its specific role in cellular responses to DNA damage is not known. Here we use Tgfβ1 knockout mice to show that radiation-induced apoptotic response is TGF-β1 dependent in the mammary epithelium, and that both apoptosis and inhibition of proliferation in response to DNA damage decrease as a function of TGF-β1 gene dose in embryonic epithelial tissues. Because apoptosis in these tissues has been shown previously to be p53 dependent, we then examined p53 protein activation. TGF-β1 depletion, by either gene knockout or by using TGF-β neutralizing antibodies, resulted in decreased p53 Ser-18 phosphorylation in irradiated mammary gland. These data indicate that TGF-β1 is essential for rapid p53-mediated cellular responses that mediate cell fate decisions in situ.

Original languageEnglish (US)
Pages (from-to)5627-5631
Number of pages5
JournalCancer research
Volume62
Issue number20
StatePublished - Oct 15 2002

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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