De novo induction of genetically engineered brain tumors in mice using plasmid DNA

Stephen M. Wiesner, Stacy A. Decker, Jon D. Larson, Katya Ericson, Colleen Forster, Jose L. Gallardo, Chunmei Long, Zachary L. Demorest, Edward A. Zamora, Walter C. Low, Karen SantaCruz, David A. Largaespada, John R. Ohlfest

Research output: Contribution to journalArticle

70 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)431-439
Number of pages9
JournalCancer Research
Volume69
Issue number2
DOIs
StatePublished - Jan 15 2009

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Brain Neoplasms
Plasmids
Oncogenes
DNA
Genes
Beauty
Neoplasms
Preclinical Drug Evaluations
DNA Transposable Elements
Astrocytoma
Glioblastoma
Glioma
Transgenic Mice
Phenotype
Brain
Research

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De novo induction of genetically engineered brain tumors in mice using plasmid DNA. / Wiesner, Stephen M.; Decker, Stacy A.; Larson, Jon D.; Ericson, Katya; Forster, Colleen; Gallardo, Jose L.; Long, Chunmei; Demorest, Zachary L.; Zamora, Edward A.; Low, Walter C.; SantaCruz, Karen; Largaespada, David A.; Ohlfest, John R.

In: Cancer Research, Vol. 69, No. 2, 15.01.2009, p. 431-439.

Research output: Contribution to journalArticle

Wiesner, SM, Decker, SA, Larson, JD, Ericson, K, Forster, C, Gallardo, JL, Long, C, Demorest, ZL, Zamora, EA, Low, WC, SantaCruz, K, Largaespada, DA & Ohlfest, JR 2009, 'De novo induction of genetically engineered brain tumors in mice using plasmid DNA', Cancer Research, vol. 69, no. 2, pp. 431-439. https://doi.org/10.1158/0008-5472.CAN-08-1800
Wiesner, Stephen M. ; Decker, Stacy A. ; Larson, Jon D. ; Ericson, Katya ; Forster, Colleen ; Gallardo, Jose L. ; Long, Chunmei ; Demorest, Zachary L. ; Zamora, Edward A. ; Low, Walter C. ; SantaCruz, Karen ; Largaespada, David A. ; Ohlfest, John R. / De novo induction of genetically engineered brain tumors in mice using plasmid DNA. In: Cancer Research. 2009 ; Vol. 69, No. 2. pp. 431-439.
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