C-Raf controlled pathways in the protection of tumor cells from apoptosis.
Int J Cancer
; 104(4): 425-32, 2003 Apr 20.
Article
em En
| MEDLINE
| ID: mdl-12584738
ABSTRACT
The Raf serine-threonine kinase is upregulated in many human tumors and plays a pivotal role in tumor cell proliferation and survival. Abrogation of c-Raf expression by specific antisense oligonucleotides (Raf-AS-ODN) efficiently blocks tumor cell growth and induces apoptosis in human cancer cells. The signaling pathways and molecular mechanisms c-Raf utilizes to mediate the survival of tumor cells are, however, not well understood. Here we show that apoptosis triggered by Raf depletion cannot be overcome by ectopic Bcl-2 expression and occurs in the absence of cytochrome c release, arguing against a direct impact of c-Raf on mitochondrial pathways of apoptosis regulation. We also show that c-Raf depletion leads to a clearly decreased expression of different epidermal growth factor (EGF) receptor ligands, suggesting that the autocrine stimulation of an EGF receptor-mediated survival pathway might be involved in the blockade of tumor cell apoptotis by c-Raf.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Apoptose
/
Proteínas Proto-Oncogênicas c-raf
/
Neoplasias
Limite:
Humans
Idioma:
En
Ano de publicação:
2003
Tipo de documento:
Article