Your browser doesn't support javascript.
loading
DNA double-strand breaks, p53, and apoptosis during lymphomagenesis in scid/scid mice.
Gurley, K E; Vo, K; Kemp, C J.
Afiliação
  • Gurley KE; Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024, USA.
Cancer Res ; 58(14): 3111-5, 1998 Jul 15.
Article em En | MEDLINE | ID: mdl-9679979
ABSTRACT
The tumor-suppressing phenotype of p53 is thought to be due to its accumulation in response to DNA damage and resultant cell cycle arrest or apoptosis. scid/scid mice are defective in DNA double-strand break repair due to a mutation in DNA-dependent protein kinase (DNAPK). Treatment of scid/scid mice with gamma radiation or N-ethyl-N-nitrosourea resulted in approximately 86% incidence of T-cell lymphomas, compared with <6% in wild-type mice. The incidence of other tumor types was not increased in scid/scid mice, suggesting that the types of DNA double-strand break that are unrepaired in these mice are not strongly carcinogenic. To determine whether mutations in DNAPK and p53 interact, we examined mice deficient in both genes. Both scid/scid p53-/- and scid/scid p53+/- mice spontaneously developed lymphomas at shorter latency than did mice with either defect alone. Loss of the wild-type p53 allele was observed in 100% of tumors from scid/scid p53 +/- mice, indicating strong selection against p53. In contrast, p53 was not inactivated in lymphomas from scid/scid p53+/+ mice. Exposure of these tumor-bearing mice to gamma radiation resulted in p53 protein accumulation and high levels of apoptosis in all tumors that were not observed in tumors from scid/scid p53+/- mice. Thus, there was a bifurcation of molecular pathways to tumorigenesis. When p53 was heterozygous in the germ line, loss of the wild-type allele occurred, and the tumors became apoptosis resistant. When p53 was wild type in the germ line, p53 was not inactivated, and the tumors remained highly apoptosis sensitive.
Assuntos
Buscar no Google
Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Linfoma de Células T / Proteína Supressora de Tumor p53 Limite: Animals Idioma: En Revista: Cancer Res Ano de publicação: 1998 Tipo de documento: Article País de afiliação: Estados Unidos
Buscar no Google
Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Linfoma de Células T / Proteína Supressora de Tumor p53 Limite: Animals Idioma: En Revista: Cancer Res Ano de publicação: 1998 Tipo de documento: Article País de afiliação: Estados Unidos