FGF-2 protects small cell lung cancer cells from apoptosis through a complex involving PKCepsilon, B-Raf and S6K2.

Patients with small cell lung cancer (SCLC) die because of chemoresistance. Fibroblast growth factor-2 (FGF-2) increases the expression of antiapoptotic proteins, XIAP and Bcl-X(L), and triggers chemoresistance in SCLC cells. Here we show that these effects are mediated through the formation of a specific multiprotein complex comprising B-Raf, PKCepsilon and ...
S6K2. S6K1, Raf-1 and other PKC isoforms do not form similar complexes. RNAi-mediated downregulation of B-Raf, PKCepsilon or S6K2 abolishes FGF-2-mediated survival. In contrast, overexpression of PKCepsilon increases XIAP and Bcl-X(L) levels and chemoresistance in SCLC cells. In a tetracycline-inducible system, increased S6K2 kinase activity triggers upregulation of XIAP, Bcl-X(L) and prosurvival effects. However, increased S6K1 kinase activity has no such effect. Thus, S6K2 but not S6K1 mediates prosurvival/chemoresistance signalling.
Mesh Terms:
Antineoplastic Agents, Apoptosis, Carcinoma, Small Cell, Cell Line, Cell Line, Tumor, Cell Survival, Drug Resistance, Neoplasm, Etoposide, Extracellular Signal-Regulated MAP Kinases, Fibroblast Growth Factor 2, Humans, Lung Neoplasms, Phosphorylation, Protein Kinase C-epsilon, Proto-Oncogene Proteins B-raf, Proto-Oncogene Proteins c-raf, Ribosomal Protein S6 Kinases, 70-kDa, Signal Transduction, X-Linked Inhibitor of Apoptosis Protein, bcl-X Protein
EMBO J.
Date: Jul. 12, 2006
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