EGFR and Tumor Suppressor Function in Brain Cancer Development

Genetically engineered mouse models (GEMM) of glioblastoma multiforme (GBM) provide a system in which de novo tumors arise and develop within the context of a proper tumor microenvironment. These models are considered superior to orthotopic xenograft systems because they allow for the development of tumors in situ and in an immune competent environment. More importantly, they allow for the assessment of specific genetic mutations on the etiology of GBM and their responses to therapeutic interventions. Using cutting edge Cre/Lox technologies, we created compound conditional transgenic strains based on a Cre-induced expression of mutant EGFRvIII with the concomitant loss of the Cdkn2a and PTEN tumor suppressor genes. The introduction of a conditional firefly luciferase transgene provides a means to monitor tumor initiation and growth noninvasively by bioluminescence imaging. The tumors that are generated in this model share numerous histopathological features with human GBMs. We provide here a detailed description of the methodologies used to initiate and monitor GBM tumors in this model system.