C-Raf controlled pathways in the protection of tumor cells from apoptosis

✍ Scribed by Emily P. Slater; Thomas Stübig; Quek Choon Lau; Tatjana V. Achenbach; Ulf R. Rapp; Rolf Müller

• Publisher: John Wiley and Sons
• Year: 2003
• Tongue: French
• Weight: 229 KB
• Volume: 104
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.10983

✦ Synopsis

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. © 2003 Wiley‐Liss, Inc.