Genetic Modeling of Glioma Formation in Mice

Begemann, Martin; Rajasekhar, Vinagolu K.; Fuller, Gregory N.; Holland, Eric C.

doi:10.1385/1-59259-843-9:055

Cited by 8 publications

(11 citation statements)

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“…Second, tumor-initiating capacity in GSCs is assessed in immunocompromised recipient mice that form tumors, lacking immunological features of clinical tumors. To address these limitations and determine whether TAZ behaves as an oncogene, we used the well-characterized RCAS/N-tva model, in which the expression of retrovirus-encoded genes can be directed to express in neural progenitor cells (NPCs) (Uhrbom and Holland 2001;Begemann et al 2002). Chicken fibroblast (DF1) cells transfected with the RCAS vector were directly injected into the brains of N-tva mice as previously described.…”

Section: Global Mes Differentiation Is Induced By Taz-tead Via Directmentioning

confidence: 99%

The transcriptional coactivator TAZ regulates mesenchymal differentiation in malignant glioma

Bhat¹,

Salazar²,

et al. 2011

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Recent molecular classification of glioblastoma (GBM) has shown that patients with a mesenchymal (MES) gene expression signature exhibit poor overall survival and treatment resistance. Using regulatory network analysis of available expression microarray data sets of GBM, including The Cancer Genome Atlas (TCGA), we identified the transcriptional coactivator with PDZ-binding motif (TAZ ), to be highly associated with the MES network. TAZ expression was lower in proneural (PN) GBMs and lower-grade gliomas, which correlated with CpG island hypermethylation of the TAZ promoter compared with MES GBMs. Silencing of TAZ in MES glioma stem cells (GSCs) decreased expression of MES markers, invasion, self-renewal, and tumor formation. Conversely, overexpression of TAZ in PN GSCs as well as murine neural stem cells (NSCs) induced MES marker expression and aberrant osteoblastic and chondrocytic differentiation in a TEAD-dependent fashion. Using chromatin immunoprecipitation (ChIP), we show that TAZ is directly recruited to a majority of MES gene promoters in a complex with TEAD2. The coexpression of TAZ, but not a mutated form of TAZ that lacks TEAD binding, with plateletderived growth factor-B (PDGF-B) resulted in high-grade tumors with MES features in a murine model of glioma. Our studies uncover a direct role for TAZ and TEAD in driving the MES differentiation of malignant glioma.

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Section: Global Mes Differentiation Is Induced By Taz-tead Via Directmentioning

confidence: 99%

The transcriptional coactivator TAZ regulates mesenchymal differentiation in malignant glioma

Bhat¹,

Salazar²,

et al. 2011

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“…The insertion or deletion of defective genes into the mouse genome provided the 'Koch's Postulates' of modern biology. 32,33 Isolation and cloning of a gene associated with human disease, when inserted into and expressed by the mouse genome, recapitulates the disease in the mouse. Clearly, one gene can cause the same disease in another species.…”

Section: Rebirth Of One Medicinementioning

confidence: 99%

“…Clearly, one gene can cause the same disease in another species. 32,33 By implication, the same disease caused by the same gene can be treated by the same medicine. Because of our ability to manipulate the genome of the laboratory mouse, the mouse has become the surrogate for human disease.…”

Section: Rebirth Of One Medicinementioning

confidence: 99%

‘One medicine—one pathology': are veterinary and human pathology prepared?

Cardiff

Ward

Barthold

2008

Laboratory Investigation

126

103

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“…Various groups, for example, have pursued transgenic strategies for inducing rodent gliomas that reflect many of the structural and histologic features of human tumors (5). Although these show promise in overcoming limitations of the xenograft approach, other discontinuities persist (6).…”

Section: Translational Models Companion Animals and Brain Cancermentioning

confidence: 99%

Faithful Companions: A Proposal for Neurooncology Trials in Pet Dogs

Kimmelman

Nalbantoglu²

2007

Cancer Research

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Although relatively rare, malignant glioma (MG) is frequently used for testing novel cancer treatments. However, human MG trials have often been initiated on the basis of preclinical models that involve numerous discontinuities with the human disease. Below, we discuss various limitations of the mainstay model used in MG preclinical research, the murine orthotopic xenograft. After discussing alternative model systems like transgenic mouse models and canine xenografts, we argue that companion animals with spontaneous brain cancers offer a scientifically and ethically attractive system for preclinical testing of novel MG interventions. Ethical advantages and practical challenges of companion animal brain cancer trials are briefly discussed. [Cancer Res 2007;67(10):4541-4]

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Genetic Modeling of Glioma Formation in Mice

Cited by 8 publications

References 0 publications

The transcriptional coactivator TAZ regulates mesenchymal differentiation in malignant glioma

The transcriptional coactivator TAZ regulates mesenchymal differentiation in malignant glioma

‘One medicine—one pathology': are veterinary and human pathology prepared?

Faithful Companions: A Proposal for Neurooncology Trials in Pet Dogs

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