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

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 journal › Article › peer-review

138 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 language	English (US)
Pages (from-to)	5627-5631
Number of pages	5
Journal	Cancer research
Volume	62
Issue number	20
State	Published - Oct 15 2002

ASJC Scopus subject areas

Oncology
Cancer Research

Cite this

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title = "Transforming growth factor-β1 mediates cellular response to DNA damage in situ",

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.",

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AU - Ewan, Kenneth B.

AU - Henshall-Powell, Rhonda L.

AU - Ravani, Shraddha A.

AU - Pajares, Maria Jose

AU - Arteaga, Carlos

AU - Warters, Ray

AU - Akhurst, Rosemary J.

AU - Barcellos-Hoff, Mary Helen

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AB - 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.

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

Abstract

ASJC Scopus subject areas

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