| 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. |