Abstract
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.
Footnotes
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵1 Funding was provided by NASA program Biomedical Research and Countermeasures Ground Research in Radiation Health, Grant T6275-W (to M. H. B. H.), NIH Grant R01 CA62212 (to C. L. A.), and Department of Defense DAMD17-01-0291 (to M. J. P.).
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↵2 To whom requests for reprints should be addressed, at Life Sciences Division, Building 74-174, 1 Cyclotron Road, Lawrence Berkeley National Laboratory, Berkeley, CA 94720. Phone: (510) 486-6371; Fax: (510) 486-6816; E-mail: MHBarcellos-Hoff{at}lbl.gov
- Received July 2, 2002.
- Accepted September 4, 2002.
- ©2002 American Association for Cancer Research.
Volume 62, Issue 20
