Entwicklung eines Astrozytom-Modells aus primären Astrozyten der Maus mit regulierbarer Proliferation

Human glioblastoma multiforme (GBM) is developing either secondary from astrocyto-ma precursors or emerges de novo. Available knowledge of the underlying molecular changes and involved pathways cannot answer many questions of gliomagenesis. Pro-gress in scientific research and multimodal treatment has as yet failed to improve substan-tially the fatal clinical outcome in these most common primary brain tumors. The new WHO classification of 2016 includes for the first time biomarkers and molecular signa-tures. There is a need for further improved models of gliomagenesis to obtain a better understanding of the etiology and to stimulate clinical advancements. In preceding studies a transformation of primary p53-knock-out-astrocyts into malignant cells was achieved by activation of myr-Akt and c-Myc. Aim of this study was the further development of the model by installing a tet-system based regulation facility to control and modify tumorigenesis in vivo. Myr-Akt and a controllable c-Myc were built in into primary p53-knock-out-astrocyts by retroviral plasmid transductions. Regulation of pro-liferation was attained by a pBabe-promotor-controlled tet-system. The used plasmids had several resistances to antibiotics for selection. In cell cultures we could verify a good controllability even in later cell passages. With these findings we added stereotactic in vivo trials with BL6 mice. It was proven that cell proliferation also in vivo could be regu-lated by tetracycline doses. The brain tumors induced by this mouse model showed much more typical features of GBM in comparison with previous models.