Oncogene-induced mitotic catastrophe and apoptosis in glioblastoma cells in vitro

Abstract

Glioblastoma (GB) is one of the most prevalent and aggressive primary brain tumour. The median survival of GB patients who underwent standard therapy (neurosurgical resection, radiotherapy and chemotherapy) is 14 months. There for, GB treatment remains a great challenge. Furthermore, in vitro culturing of glioblastoma cells constitutes problematic issue. The reason for these difficulties might be found in 3 processes that were observed during in vitro cell culturing: apoptosis, mitotic catastrophe and senescence. The spontaneous occurrence of these phenomena leads to inhibition of cell division and / or cell death. Only a small percentage of glioblastoma cases present a genetic predisposition to be cultured in vitro. Analysis of available date indicate that 50% of GB cell lines are characterised by the coexistence of TP53 mutations and CDKN2A deletions. Comparing this percentage to 5% of coexistence of above-mentioned genetic changes in samples collected from patients (presenting) we can presume that the presence of those alterations has impact on stabilization of glioblastoma cell cultures. Importantly, proteins p16, p14 (encoded by CDKN2A) and TP53 protein are involved in the mentioned processes. In vitro dominates, senescence, apoptosis and mitotic catastrophe of glioblastoma cells. Identification of factors, responsible for spontaneous inhibition of cell division and / or cell death of glioblastoma cells in vitro, may provide a ground for a new GB therapeutic approach.