Transforming growth factor-beta1 mediates cellular response to DNA damage in situ.
Cancer Res
; 62(20): 5627-31, 2002 Oct 15.
Article
em En
| MEDLINE
| ID: mdl-12384514
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.
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Base de dados:
MEDLINE
Assunto principal:
Dano ao DNA
/
Proteína Supressora de Tumor p53
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Fator de Crescimento Transformador beta
Idioma:
En
Ano de publicação:
2002
Tipo de documento:
Article