Glioblastoma multiforme (GBM) is a primary CNS neoplasm and the most common, aggressive and malignant brain tumour in adults. Even though many studies have been performed on its pathological genetics and molecular pathways, there is currently no possible cure. The aim of this study was to investigate the role of the serine/threonine kinase homeodomain interacting protein kinase 2 (HIPK2) in the pathology of GBM. A variety of experimental approaches revealed strong variations in HIPK2 protein expression levels. My work showed that these expression changes are due to a variety of factors including gene amplification (U373 and U87 cells), mRNA expression and protein stabilities. Further proliferation experiments showed that GBM cell lines (U373, U87 and U118 cells) stop growth upon the lentiviral HIPK2-knockdown. These results suggest that at least some GBMs depend on HIPK2 for their proliferation. In parallel, this study analyzed the functional consequences of HIPK2 mutations that were detected in tumour cells. HIPK2 expression vectors carrying these mutations were generated and tested for their localization, kinase activity and for their ability to interact with the SUMO protein and the prolyl isomerase PIN1. No major differences in all these parameters were observed - this suggests that the functional role of HIPK2 in oncogenesis is due to its relative expression levels.
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