Abstract 1554: Inducible B-Raf and c-Src models as tools for drug development

• Published in: Cancer research (Chicago, Ill.) Ill.), 2013-04, Vol.73 (8_Supplement), p.1554-1554
• Main Authors: Ehlert, Jan E., Mutschler, Bettina, Mueller, Melanie, Lingnau, Andreas, Hoffmann, Steffen, Weber, Holger, Kubbutat, Michael H. G.
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2013-1554

C-Src and B-Raf are critical kinases in signal transduction often involved in the onset of cancer and therefore representing promising targets for drug development. In order to assess the kinase-specific inhibitory effect in cellular and in-vivo models, we have generated cell lines exogenously expressing either c-Src or the commonly found mutant B-RafV600E in a regulatable manner, either by Doxicyclin-suppression or Hydroxy-Tamoxifen activation, respectively. Despite moderate kinase expression levels we observe significantly increased kinase activity in the activated state which can be monitored by substrate specific phospho-ELISAs as well as by analysis of phenotypic responses such as soft agar growth. Moreover, these cellular models are applicable for in-vivo analyses, showing strong in vivo growth in the activated state while no tumor growth occurs in the unactivated state. The applicability of these models in drug development is exemplified using c-Src inhibitor Dasatinib and B-Raf inhibitor Sorafenib. Citation Format: Jan E. Ehlert, Bettina Mutschler, Melanie Mueller, Andreas Lingnau, Steffen Hoffmann, Holger Weber, Michael H. G. Kubbutat. Inducible B-Raf and c-Src models as tools for drug development. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1554. doi:10.1158/1538-7445.AM2013-1554