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Publication : Transforming growth factor-beta1 mediates cellular response to DNA damage in situ.

First Author  Ewan KB Year  2002
Journal  Cancer Res Volume  62
Issue  20 Pages  5627-31
PubMed ID  12384514 Mgi Jnum  J:79759
Mgi Id  MGI:2388896 Citation  Ewan KB, et al. (2002) Transforming Growth Factor-beta1 Mediates Cellular Response to DNA Damage in Situ. Cancer Res 62(20):5627-31
abstractText  Transforming growth factor (TGF)-beta1 is rapidly activated after ionizing radiation, but its specific role in cellular responses to DNA damage is not known. Here we use Tgfbeta1 knockout mice to show that radiation-induced apoptotic response is TGF-beta1 dependent in the mammary epithelium, and that both apoptosis and inhibition of proliferation in response to DNA damage decrease as a function of TGF-beta1 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-beta1 depletion, by either gene knockout or by using TGF-beta neutralizing antibodies, resulted in decreased p53 Ser-18 phosphorylation in irradiated mammary gland. These data indicate that TGF-beta1 is essential for rapid p53-mediated cellular responses that mediate cell fate decisions in situ.
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