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 journalArticle

124 Citations (Scopus)

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

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Transforming Growth Factors
DNA Damage
Epithelium
Apoptosis
Gene Knockout Techniques
Human Mammary Glands
Ionizing Radiation
Neutralizing Antibodies
Knockout Mice
Breast
Phosphorylation
Radiation
Genes
Proteins

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Ewan, K. B., Henshall-Powell, R. L., Ravani, S. A., Pajares, M. J., Arteaga, C., Warters, R., ... Barcellos-Hoff, M. H. (2002). Transforming growth factor-β1 mediates cellular response to DNA damage in situ. Cancer Research, 62(20), 5627-5631.

Transforming growth factor-β1 mediates cellular response to DNA damage in situ. / Ewan, Kenneth B.; Henshall-Powell, Rhonda L.; Ravani, Shraddha A.; Pajares, Maria Jose; Arteaga, Carlos; Warters, Ray; Akhurst, Rosemary J.; Barcellos-Hoff, Mary Helen.

In: Cancer Research, Vol. 62, No. 20, 15.10.2002, p. 5627-5631.

Research output: Contribution to journalArticle

Ewan, KB, Henshall-Powell, RL, Ravani, SA, Pajares, MJ, Arteaga, C, Warters, R, Akhurst, RJ & Barcellos-Hoff, MH 2002, 'Transforming growth factor-β1 mediates cellular response to DNA damage in situ', Cancer Research, vol. 62, no. 20, pp. 5627-5631.
Ewan KB, Henshall-Powell RL, Ravani SA, Pajares MJ, Arteaga C, Warters R et al. Transforming growth factor-β1 mediates cellular response to DNA damage in situ. Cancer Research. 2002 Oct 15;62(20):5627-5631.
Ewan, Kenneth B. ; Henshall-Powell, Rhonda L. ; Ravani, Shraddha A. ; Pajares, Maria Jose ; Arteaga, Carlos ; Warters, Ray ; Akhurst, Rosemary J. ; Barcellos-Hoff, Mary Helen. / Transforming growth factor-β1 mediates cellular response to DNA damage in situ. In: Cancer Research. 2002 ; Vol. 62, No. 20. pp. 5627-5631.
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