Systems biology study of astrocytomagenesis

在条件突变小鼠（T、TR、TRP）的3月龄成年星形胶质细胞中诱导致癌事件。在诱导后的不同时间点，将突变小鼠沿着与不携带GFAP-CreER ™转基因的他莫昔芬处理的对照一起处死，并收集血清和脑样品用于进一步分析。脑样本根据其基因型和病理分组，并用于基因表达微阵列分析（与L。Hood，Institute for Systems Biology in西雅图，WA）和建立细胞系用于进一步的功能分析。系统方法已被应用于确定参与星形细胞瘤的启动和进展的关键分子网络。对微阵列数据的初步分析表明，在肿瘤发生和发展过程中，分子网络发生了动态变化。我们最初专注于表达随着肿瘤分级逐渐增加的基因集。这些基因参与介导DNA复制和修复（例如Gins 1、Dna 2）、细胞分裂和染色体传递保真度（例如Aspm）、转录调节（例如Olig 2）、免疫应答信号传导、干细胞和祖细胞生物学以及其他过程的几个关键分子网络。选择的基因集将用于体外和体内功能分析。描述这些研究的手稿正在准备出版。

Oncogenic events were induced in the adult astrocytes of conditional mutated mice (T, TR, TRP) at 3 months of age. Mutant mice along with tamoxifen-treated controls that did not carry GFAP-CreERTM transgene were sacrificed at different time points after induction and blood serum and brain samples were collected for further analysis. Brain samples were grouped according to their genotype and pathology and used for gene expression microarray analysis (collaboration with L. Hood, Institute for Systems Biology in Seattle, WA) and establishment of cell lines for further functional analysis. The systems approach has been applied to identify key molecular networks involved in astrocytoma initiation and progression. Initial analysis of the microarray data demonstrated dynamic changes of molecular networks during tumor initiation and progression. We initially focused on gene sets which expression gradually increases with tumor grade. These genes were involved in several key molecular networks that mediate DNA replication and repair (e.g. Gins1, Dna2), cell division and chromosome transmission fidelity (e.g. Aspm), regulation of transcription (e.g. Olig2), immune response signaling, stem and progenitor cell biology, and other processes. Selected gene sets will be used for functional analysis in vitro and in vivo. A manuscript describing these studies is in preparation for publication.