Quantitaive analysis of signalling pathways using protein microarrays

Coordinator:		Dr. Ulrike Korf
Institution:		Deutsches Krebsforschungszentrum
Homepage:		www.dkfz.de/

Cancer can be defined as a deregulation of physiological processes regulating cellular proliferation, differentiation, and apoptosis. The physiological balance is maintained through tightly regulated and interconnected processes frequently mediated by protein phosphorylation and de-phosphorylation events. Well-known examples for cancer-relevant signaling cascades are the MAPK- or JAK/STAT-pathways, which, in turn are influenced by oncogenes (e. g. RAS) or membrane-bound receptors (e. g. EGFRs or other receptor tyrosine kinases). The first goal of this subproject is therefore to determine the activation status of cancer–related signalling pathways in tumors and to compare the proteome profiling data with clinical parameters. Proteome profiling will be done in a multiplex format employing the established reverse phase protein array (RPPA) technology.
In the clinical routine, prostate cancer is initially diagnosed by elevated levels of  PSA in the serum of patients. Nevertheless, elevated levels of PSA do not reliably indicate the presence of a tumor and more reliable indicators are required for the diagnosis of prostate cancer.
An additional objective is the idenfification of new prostate cancer markers compatible with minimally invasive methods. For this reason we will set up technologies to identify new marker proteins (e.g. proteolysis products) in serum and to develop antibody-based detection systems to validate newly identified marker proteins in a larger set of serum samples.