BCL-xL: time-dependent dissociation between modulation of apoptosis and invasiveness in human malignant glioma cells.
Cell Death Differ
; 13(7): 1156-69, 2006 Jul.
Article
em En
| MEDLINE
| ID: mdl-16254573
ABSTRACT
Conditionally BCL-xL-overexpressing LNT-229 Tet-On glioma cell clones were generated to investigate whether the 'antiapoptosis phenotype' and the 'motility phenotype' mediated by BCL-2 family proteins in glioma cells could be separated. BCL-xL induction led to an immediate and concentration-dependent protection of LNT-229 cells from apoptosis. BCL-xL induction for up to 3 days did not result in altered invasiveness. In contrast, long-term BCL-xL induction for 21 days resulted in increased transforming growth factor-beta2 expression, and in metalloproteinase-2 and -14 dependent, but integrin independent, increased invasiveness. Withdrawal of doxycycline (Dox) abolished the protection from apoptosis whereas the 'invasion phenotype' remained stable. Dox stimulation of BCL-xL-inducible LNT-229 cells conferred infiltrative growth to BCL-xL-positive glioma cells in vivo and reduced the survival of tumor-bearing mice. These data allow to dissect a direct antiapoptotic action of BCL-xL from an indirect effect, presumably mediated by altered gene expression, which modifies tumor cell invasiveness in vitro and in vivo.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Movimento Celular
/
Apoptose
/
Proteína bcl-X
/
Glioma
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Cell Death Differ
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Alemanha