Loss of wild-type p53 bestows a growth advantage on primary cortical astrocytes and facilitates their in vitro transformation.
Cancer Res
; 55(13): 2746-51, 1995 Jul 01.
Article
em En
| MEDLINE
| ID: mdl-7796398
ABSTRACT
Primary cortical astrocytes were isolated from normal (+/+), heterozygous (+/-), or homozygous (-/-) p53-knockout mice. The normal astrocytes grew slowly and underwent crisis after limited division, while the homozygously defective cells grew rapidly and without contact inhibition. These -/- cells could not initially form colonies in soft agarose but acquired this capability after 10 passages in FCS or basic fibroblast growth factor but not epidermal growth factor. Almost all -/- astrocytes weakly expressed glial fibrillary acidic protein at passage 10 and were also A2B5+ when cultured in basic fibroblast growth factor. Most heterozygous cells resembled normal ones; however, some survived crisis, grew rapidly, and formed colonies. Outgrowing cells had all lost the wild-type p53 allele. These molecular and cellular events mimic the early stages of human brain tumors, suggest a role for p53 in the earliest stages of disease progression, and provide an experimental system to analyze the effects of other tumor-specific mutations in the disease process.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Córtex Cerebral
/
Astrócitos
/
Genes p53
Limite:
Animals
Idioma:
En
Ano de publicação:
1995
Tipo de documento:
Article