Gene expression data from transgenic and knockout mice
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE64756 | GEO | 2015/01/08
SECONDARY ACCESSION(S): PRJNA271799
REPOSITORIES: GEO
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Project description:Activation of oncogenic ras pathway accounts for up to 90% low-grade superficial urothelial carcinomas of bladder, and p53 deficiency is very common in high-grade muscle invasive carcinomas. These two pathways in bladder urothelial tumorigenesis used to be considered divergent and their potential collaboration has not been illustrated. We did laser capture micro-dissection (LCM) to separate the tumor cells from the whole bladder tissues from H-ras transgenic and p53 knockout mice, as well as normal urothelial cells as control. Microarray was then performed to identify distinct classes of up-regulated genes during tumorigenesis and progression. In order to get the gene expression profiles of carcinoma in situ (CIS), muscle invasive tumors and normal cells, we used LCM to purify the cells from mixture of different types of cells, and then extracted RNA for microarray. There are three groups applied in microarray, which are normal cells as control, CIS (tumor genesis) and invasive tumors (tumor progression).
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Project description:Bladder cancer (BC) is a highly prevalent human disease in which Rb pathway inactivation and epigenetic alterations are common events. However, the connection between these two processes is still poorly understood. Here we show that the in vivo inactivation of all Rb family genes in the mouse urothelium is sufficient to initiate BC development. The characterization of the mouse tumors revealed multiple molecular features of human BC, including the activation of E2F transcription factor and subsequent Ezh2 expression, and the activation of several signaling pathways previously identified as highly relevant in urothelial tumors. Whole transcriptional characterizations of the mouse bladder tumors revealed a significant overlap with human BC samples, and a predominant role for Ezh2 in the downregulation of gene expression programs. Importantly, we determined that in human superficial BC patients, the increased tumor recurrence and progression in these recurrences is associated with increased E2F and Ezh2 expression and Ezh2-mediated gene expression repression. Collectively, our studies provide a genetically defined model for human high-grade superficial BC and demonstrate the existence of an Rb-E2F-Ezh2 axis in bladder whose disruption can promote tumor development. Gene expression was analyzed in normal bladder and bladder tumours, both in humans and in transgenic mice.
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Project description:Somatic mutations of the fibroblast growth factor receptor 3 (FGFR3) are one of the most frequent genetic alterations in bladder carcinomas. We report here that human-FGFR3-S249C expression in urothelial cells of transgenic mice induces low-grade papillary tumors presenting genomic instability and resembling human pTa urothelial tumors at the transcriptomic level. Mutated-FGFR3 expression levels impacted the incidence of tumor formation and could account for the tissue specificity of human mutated FGFR3-driven tumors restricted to epithelia presenting high normal expression levels of FGFR3.
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Project description:Here we report the discovery of truncating mutations of the gene encoding the cohesin subunit STAG2, which regulates sister chromatid cohesion and segregation, in 36% of papillary non-invasive urothelial carcinomas and 16% of invasive urothelial carcinomas of the bladder. Our studies suggest that STAG2 has a role in controlling chromosome number but not the proliferation of bladder cancer cells. These findings identify STAG2 as one of the most commonly mutated genes in bladder cancer. Affymetrix CytoScan HD Arrays were performed according to the manufacturer's directions on genomic DNA extracted directly from 12 snap-frozen human urothelial carcinoma primary tumors with somatic mutations of the STAG2 gene.
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