Apoptosis caused by chemotherapeutic inhibition of nuclear factor-kappaB activation.
Cancer Res
; 63(2): 290-5, 2003 Jan 15.
Article
en En
| MEDLINE
| ID: mdl-12543776
ABSTRACT
Both the protein kinase C (alpha/beta) inhibitor Go6976 and expression of dominant-negative nuclear factor (NF)-kappaB inhibitor kinase mutants (a) blocked the growth and caused regression of a mammary tumor insyngeneic mice; (b) inhibited epidermal growth factor (EGF)-induced activation, nuclear translocation, and DNA-binding activity of NF-kappaB; and (c) caused apoptosis of EGF-stimulated cultured mammary tumor cells. cDNA microarray analysis revealed that these treatments reversed the expression changes of a subset of genes altered by EGF treatment. These included up-regulation of proapoptotic genes of the tumor necrosis factor (TNF) pathway, death-associated protein (DAP) kinase, p53, and p21/Waf1; and down-regulation of inhibitors of apoptosis inhibitor of apoptosis(IAP)-1 and X-IAP, TNF receptor-associated factor (TRAF)-2, and factors OX40 and 4-1BB. These results and our previous studies suggest the practicality of a target-directed chemotherapy for EGF-responsive breast cancers, by blocking NF-kappaB activation and thereby reinstating apoptosis.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Carbazoles
/
Adenocarcinoma
/
FN-kappa B
/
Proteínas Serina-Treonina Quinasas
/
Apoptosis
/
Indoles
/
Neoplasias Mamarias Experimentales
Límite:
Animals
Idioma:
En
Revista:
Cancer Res
Año:
2003
Tipo del documento:
Article
País de afiliación:
Estados Unidos