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

Pardo, O.E., Wellbrock, C., Khanzada, U.K., Aubert, M., Arozarena, Imanol, Davidson, S., Bowen, F., Parker, P.J., Filonenko, V.V., Gout, I.T., Sebire, N., Marais, R., Downward, J. and Seckl, M.J. (2006) FGF-2 protects small cell lung cancer cells from apoptosis through a complex involving PKCepsilon, B-Raf and S6K2. Embo Journal, 25 (13). pp. 3078-3088. ISSN 0261-4189

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Abstract

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.

Item Type: Article
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Schools: School of Applied Sciences
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Depositing User: Imanol Arozarena Arozarena
Date Deposited: 03 Mar 2015 15:21
Last Modified: 03 Mar 2015 15:21
URI: http://eprints.hud.ac.uk/id/eprint/23409

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