Cell cycle arrest is sufficient for p53-mediated tumor regression.
Gene Ther
; 8(22): 1705-12, 2001 Nov.
Article
em En
| MEDLINE
| ID: mdl-11892838
ABSTRACT
p53 gene therapy can induce tumor regression, but the low efficacy of in vivo gene transfer has greatly hampered the mechanistic analysis of this antitumoral activity. We therefore used a p53-null human NSCLC cell line in which we reintroduced the wild-type p53 gene under control of a tetracycline-dependent promoter. P53 induction provokes cell cycle arrest in G0/G1 and G2/M phase, an up-regulation of p21, a down-regulation of cyclin B1 and appearance of senescence features without down-regulation of human telomerase reverse transcriptase. No detectable morphological changes of apoptosis nor procaspase-3 activation are observed. In subcutaneous tumors grafted in nude mice, the induction of p53 expression leads to a complete and longlasting tumor regression in 28 days which is associated with cell cycle arrest, but not detectable apoptosis nor inhibition of angiogenesis. These results show that irreversible cell cycle arrest is sufficient to elicit tumor regression after p53 gene transfer in p53-deficient tumor cells.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Terapia Genética
/
Genes p53
/
Carcinoma Pulmonar de Células não Pequenas
/
Neoplasias Pulmonares
Limite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Gene Ther
Assunto da revista:
GENETICA MEDICA
/
TERAPEUTICA
Ano de publicação:
2001
Tipo de documento:
Article
País de afiliação:
França