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 |
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ASJC Scopus subject areas
- Oncology
- Cancer Research
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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 journal › Article
}
TY - JOUR
T1 - Transforming growth factor-β1 mediates cellular response to DNA damage in situ
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
PY - 2002/10/15
Y1 - 2002/10/15
N2 - 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.
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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UR - http://www.scopus.com/inward/citedby.url?scp=0037108674&partnerID=8YFLogxK
M3 - Article
C2 - 12384514
AN - SCOPUS:0037108674
VL - 62
SP - 5627
EP - 5631
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0099-7013
IS - 20
ER -