Signalling Networks

D. Arlt, Ö. Sahin, S. Uhlmann, A. Ward, , C. Horwedel, I. Keklikoglou, S. Wagner, A. Ward, Christina Bootz, Sandra Blaszkiewicz, Sara Burmester (DKFZ)

Regulation of the cell cycle in breast cells encloses complex mechanisms of protein networks involving distinct cellular processes. In these networks, cross talk between growth factor and hormone receptor signalling is causatively associated with sensitivity and resistance to therapies in breast cancer. We will model and experimentally refine a network to elucidate the bypass mechanisms of cell growth inhibition after drug treatment with subproject "Network reconstruction". As network components, we have chosen key receptors, key signal transduction intermediates and cell cycle regulators. This network will be extended with validated assays hits in NGFNplus. Different breast cancer cell lines and tamoxifen resistant cells will serve as model systems in which we determine the G1/S phase transition. Utilizing RNAi we will produce single and multiple knock-downs of network elements to examine their effects on cell growth. Finally, we will check our cell cycle model by comparing computer-based simulations with the experimental counterparts. Our aim is to identify key proteins and cross-talk events for novel therapeutic strategies in breast cancer.