Ewan, Kenneth ORCID: https://orcid.org/0000-0001-6622-9009, Henshall-Powell, R. L., Ravani, S. A., Tang, Y., Akhurst, R., Wakefield, L. and Barcellos-Hoff, M. H. 2002. Transforming growth factor-beta1 mediates cellular response to DNA damage in situ. Cancer Research 62 (20) , pp. 5627-5631. |
Abstract
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.
Item Type: | Article |
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Date Type: | Publication |
Status: | Published |
Schools: | Biosciences |
Publisher: | American Association for Cancer Research |
ISSN: | 0008-5472 |
Last Modified: | 27 Oct 2022 09:27 |
URI: | https://orca.cardiff.ac.uk/id/eprint/65905 |
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