Funktionelle Charakterisierung der Kinasen IRAK1, TTK, SGK1, TBK1 und PRKDC im Pankreaskarzinom

Abstract The diagnosis of pancreatic cancer still remains related with poor diagnosis, since it is known for its early metastasis and its inapparent growth without any sufficient therapy strategies. These facts implicate the need for more research concerning the treatment of pancreatic cancer. In this thesis five different human kinases, IRAK1, TTK, SGK1, TBK1 and PRKDC have been analyzed concerning their function and their importance in cell lines of pancreatic cancer. Especially cancer specific characteristics like proliferation, the capability of migration and metastasis as well as the inhibition of apoptosis were examined. The aim of this thesis was to identify a kinase, which could be inhibited by a targeted-therapy against pancreatic cancer. While the inhibition of the kinases TBK1 and PRKDC did not show any desirable effects on proliferation, the repression of the kinase SGK1 resulted in the global inhibition of proliferation of all cell lines including also the benign cellline. This is the reason why these three kinases were excluded from the following experiments. The repression of the kinase IRAK1 as well as the repression of the kinase TTK resulted in an inhibition of proliferation plus an induction of apoptosis, where the effect of TTK repression was greater than of IRAK1 repression. It should be noted that the kinase TTK showed the greatest effect in all experiments, except for the migration assay. Consequently TTK seems to play a crucial role in proliferation, in inhibition of apoptosis as well as in the ability of metastasis of pancreatic cancer. These findings suggest the kinase TTK as a potential target regarding a new chemotherapy-option against the ductal adenocarcinoma of pancreas, which should be further examined.