RT Journal Article
SR Electronic
T1 Transforming Growth Factor-β1 Mediates Cellular Response to DNA Damage <strong><em>in Situ</em></strong>
JF Cancer Research
JO Cancer Res
FD American Association for Cancer Research
SP 5627
OP 5631
VO 62
IS 20
A1 Ewan, Kenneth B.
A1 Henshall-Powell, Rhonda L.
A1 Ravani, Shraddha A.
A1 Pajares, Maria Jose
A1 Arteaga, Carlos
A1 Warters, Ray
A1 Akhurst, Rosemary J.
A1 Barcellos-Hoff, Mary Helen
YR 2002
UL http://cancerres.aacrjournals.org/content/62/20/5627.abstract
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.