肿瘤基因组图谱及功能系统生物学.ppt

* * * * * * * * * * * * * Flow and distribution of biomolecules from BCR to TCGA centers for analyses. Flow chart showing the TCGA glioblastoma molecular analyses and their evaluation after provision of specimens and clinical data by the Biospecimen Core Resource (BCR) (see Figure S1). The data obtained from multiple analysis platforms is evaluated by multiple institutions and integrated to form a global representation of the genomic and transcriptomic alterations that occur in glioblastoma. * * * This paper formed the foundation for the later publications directly or indirectly using TCGA data. Almost the signature genes or pathways claimed by the later papers more or less have been mentioned in this paper. * * There are 3 Akt isoforms, Akt1, 2, and 3. They are located on different chromosomes, but share high degree of homology. * * Mouse KO studies have given us an understanding of the developmental roles of the isoforms. ….so these studies indicate that there are non-redundant roles of the isoforms. * * Akt is one of the most frequently… Absence of Akt1 mutations in glioblastoma (Plos One 2009) * * To understand more about the Akt isoforms in glioma, we compared gene expression levels of each Akt in normal human brain to Oligo/AO. ….these data indicated that there the Akts may play different roles in glioma. * * * * The tumors generated from these mice closely recapitulate human glioma and can be graded according to WHO criteria. * * To evaluate the differences in the Akt isoforms, we injected GFP alone, PDGFB alone, or in combo with Akt1, 2, or 3. * * * * * * * * * * * * * * * * * * * * 肿瘤组织需要更多营养 胶质瘤血管丰富 VEGF表达增高 VEGF蛋白分泌出细胞外并与血管内皮细胞受体结合，促进其的生长 GRB2 FGF7 FSHR PTK7 VEGF 成纤维细胞生长因子家族成员 卵泡刺激素 受体 酪氨酸激酶 所有4个基因的蛋白产物是细胞信号转导通路的一部分，涉及酪氨酸激酶表面受体 这些受体被激活后，通过一系列转换蛋白的信号传递到下游分子 GRB2是已经确定的最关键的连接蛋白之一 GRB2也是干预肿瘤的靶点，因为它链接到多个生长因子信号转导通路. GRB2 GNB2 分子生物学研究表明，活化的酪氨酸激酶受体蛋白GRB-2能激活ras-MAP kinase-NF?B 信号通路，从而完成从细胞外到细胞核的信号传递 GNB2 是 ras 家族成员之一 MAP kinase 1 c-rel GNB2 调控 MAP 激酶 1,