A novel complex comprising BRaf, PKCϵ and S6K2 mediates the pro-survival effects of FGF-2 in small cell lung cancer cells

摘要: AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA 2522 Patients with small cell lung cancer (SCLC) die because of chemoresistance. We have previously shown that fibroblast growth factor-2 (FGF-2) increases the translation and thereby expression antiapoptotic proteins, XIAP Bcl-XL triggers chemoresistance in SCLC cells. Here we show these effects are mediated through formation a specific multi-protein complex comprising B-Raf, PKCϵ S6K2. S6K1, Raf-1 other PKC isoforms do not form similar complexes. RNAi-mediated downregulation or S6K2 abolishes FGF-2-mediated survival. In contrast, over-expression levels tetracycline-inducible system, increased kinase activity upregulation XIAP, pro-survival effects. However, S6K1 has no such effect. The prosurvival this were also seen HEK293 Moreover, RNAi knockdown but impaired clonogenic breast non-small Thus, mediates pro-survival/chemoresistance signalling. Intriguingly, immunohistochemical biopsy specimens appeared to correlate subsequent resistance therapy. conclusion, pathway may predict provide new targets for novel therapeutics.