De novo Induction of Genetically Engineered Brain Tumors in Mice Using Plasmid DNA
Open Access
- 15 January 2009
- journal article
- Published by American Association for Cancer Research (AACR) in Cancer Research
- Vol. 69 (2), 431-439
- https://doi.org/10.1158/0008-5472.can-08-1800
Abstract
Spontaneous mouse models of cancer show promise to more accurately recapitulate human disease and predict clinical efficacy. Transgenic mice or viral vectors have been required to generate spontaneous models of glioma, a lethal brain tumor, because nonviral gene transfer is typically transient. To overcome this constraint, we used the Sleeping Beauty transposable element to achieve chromosomal integration of human oncogenes into endogenous brain cells of immunocompetent mice. Genetically engineered, spontaneous brain tumors were induced with plasmid DNA in a matter of weeks in three separate mouse strains. The phenotype of tumors was influenced by the combination of oncogenes delivered, resembling human astrocytoma or glioblastoma in the majority of cases. At least five different genes can be cotransfected simultaneously including reporters, allowing measurement of tumor viability by in vivo imaging. This model can accelerate brain tumor research in a variety of ways such as generation of “humanized” models for high throughput drug screening and candidate gene validation with exceptional speed and flexibility. [Cancer Res 2009;69(2):431–9]Other Versions
This publication has 51 references indexed in Scilit:
- Spontaneous immune responses against glioma-associated antigens in a long term survivor with malignant gliomaJournal of Translational Medicine, 2007
- Toll-like receptor 4–dependent contribution of the immune system to anticancer chemotherapy and radiotherapyNature Medicine, 2007
- The 2007 WHO Classification of Tumours of the Central Nervous SystemActa Neuropathologica, 2007
- CD133+ and CD133− Glioblastoma-Derived Cancer Stem Cells Show Differential Growth Characteristics and Molecular ProfilesCancer Research, 2007
- Nf1 expression is dependent on strain background: implications for tumor suppressor haploinsufficiency studiesneurogenetics, 2007
- Sensitive mutation detection in heterogeneous cancer specimens by massively parallel picoliter reactor sequencingNature Medicine, 2006
- Probing tumor phenotypes using stable and regulated synthetic microRNA precursorsNature Genetics, 2005
- Somatic Induction of Pten Loss in a Preclinical Astrocytoma Model Reveals Major Roles in Disease Progression and Avenues for Target Discovery and ValidationCancer Research, 2005
- Radiotherapy plus Concomitant and Adjuvant Temozolomide for GlioblastomaThe New England Journal of Medicine, 2005
- Initial sequencing and analysis of the human genomeNature, 2001