SULM – Schweizerische Union für Labormedizin | Union Suisse de Médecine de Laboratoire | Swiss Union of Laboratory Medicine

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C Meier1 , A Arcaro2

1Division of Clinical Chemistry and Biochemistry, Department of Pediatrics, University of Zurich, Steinwiesstr.75, 8032 Zurich, email: Cette adresse e-mail est protégée contre les robots spammeurs. Vous devez activer le JavaScript pour la visualiser. , 2Division of Clinical Chemistry and Biochemistry, Department of Pediatrics, University of Zurich, Zurich, Switzerland

Small cell lung cancer (SCLC) accounts for 20-25% of all lung cancers and is the most severe one with a 5-year survival rate of 1-2%. Investigations into the mechanisms involved in the development of this cancer may result in the development of new strategies for therapies. It has been shown that SCLC cell lines overexpress phosphoinositide 3-kinases (PI3Ks)(1) which, in addition, show enhanced activities in a wide range of other tumor types. There are eight known isoforms in humans but their individual functions remain poorly understood. This study is focused mainly on three of them, namely p110α, p110β and PI3KC2β. Their individual effects on cell growth, proliferation, motility and apoptosis will be studied in SCLC cell lines. For this purpose, cell lines stably expressing these proteins are currently being generated. Dominant negative mutants and RNA interference (RNAi) will also be expressed to test if cell growth, proliferation and motility are reduced and/or apoptosis is induced. The stimulation of SCLC by growth factors will also be investigated. Preliminary results show that Akt (protein kinase B, PKB), a downstream target of PI3Ks, is activated in SCLC by stem cell factor (SCF) as was also shown before (1). The activation of the PI3K pathway can also be nicely shown in COS cells using EGF as stimulator. The results of our studies will give novel insights into the involvement of this signalling pathway in human cancer and may give some hints for new anti-cancer strategies.

1. Arcaro A, Khanzada UK, Vanhaesebroeck B, Tetley TD, Waterfield MD, Seckl MJ. EMBO J. 2002 Oct 1; 21(19): 5097-108.

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