PT  - JOURNAL ARTICLE
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
TI  - Transforming Growth Factor-β1 Mediates Cellular Response to DNA Damage <strong><em>in Situ</em></strong>
DP  - 2002 Oct 15
TA  - Cancer Research
PG  - 5627--5631
VI  - 62
IP  - 20
4099  - http://cancerres.aacrjournals.org/content/62/20/5627.short
4100  - http://cancerres.aacrjournals.org/content/62/20/5627.full
SO  - Cancer Res2002 Oct 15; 62
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. ©2002 American Association for Cancer Research.