Over-expression of p53 mutants in LNCaP cells alters tumor growth and angiogenesis in vivo.
Biochem Biophys Res Commun
; 345(3): 1207-14, 2006 Jul 07.
Article
em En
| MEDLINE
| ID: mdl-16723121
ABSTRACT
This study has investigated the impact of three specific dominant-negative p53 mutants (F134L, M237L, and R273H) on tumorigenesis by LNCaP prostate cancer cells. Mutant p53 proteins were associated with an increased subcutaneous "take rate" in NOD-SCID mice, and increased production of PSA. Tumors expressing F134L and R273H grew slower than controls, and were associated with decreased necrosis and apoptosis, but not hypoxia. Interestingly, hypoxia levels were increased in tumors expressing M237L. There was less proliferation in F134L-bearing tumors compared to control, but this was not statistically significant. Angiogenesis was decreased in tumors expressing F134L and R273H compared with M237L, or controls. Conditioned medium from F134L tumors inhibited growth of normal human umbilical-vein endothelial cells but not telomerase-immortalized bone marrow endothelial cells. F134L tumor supernatants showed lower levels of VEGF and endostatin compared with supernatants from tumors expressing other mutants. Our results support the possibility that decreased angiogenesis might account for reduced growth rate of tumor cells expressing the F134L p53 mutation.
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Coleções:
01-internacional
Temas:
Geral
/
Tipos_de_cancer
/
Outros_tipos
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Próstata
/
Genes p53
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Proteína Supressora de Tumor p53
/
Neoplasias
/
Neovascularização Patológica
Limite:
Humans
/
Male
Idioma:
En
Revista:
Biochem Biophys Res Commun
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Austrália