| Tumors are usually the result of a loss of control of cell growth. Many genes are potentially involved in this process. They may be activated or upregulated, which are the proto-oncogenes. Alternatively, they are found inactivated and act as tumor suppressers. Various screens are being performed to identify such genes. These include screens with retroviral libraries or through viral insertion. Many genes have been identified through these technologies. A large portion of these genes code for kinases or phosphatases that are probably involved in controlling various signal transduction pathways. The cell biology of signal transduction is prominent part within Theme 1b. Studies concentrate on signalling through growth factor receptors, through mitogenic phospholipids, but also through the estrogen receptor. The down stream effectors are also studied. These can be immediately downstream of such receptors, like the effects on the MAPkinase pathway, but also more downstream effectors resulting in activation of Polo-kinases, caspases or transcription factors. These processes control cell division, death and growth. To become activated, or to terminate activation of a growth factor receptor, receptors have to be internalised and degraded. How this pathway is controlled is studied at the cell biological and electron-microscopical level. Novel techniques are developed to follow these processes at the single cell level, employing fluorescence and various microscopical techniques including FRAP, FLIP and FRET. To execute cell division, a number of processes are crucial, like cytoskeletal changes and motor protein activation. These are controlled by various factors like the small GTPases and are studied by various groups within this Theme. In order to migrate (to form metastasis), cells have to alter their adhesion to the cell substratum and move in a particular direction. These processes are controlled by adhesion molecules and chemokines, also studied here. Various targets are identified for either inhibition by small molecular compounds or immunotherapy. Immunotherapy by genetically modified T cells, by activation of the immune response and by antibodies, are all developed and tested for applicability. |
