Gliomas are the most common primary tumors in the brain. They are divided into different clinical grades on base of their histology and prognosis. The most malignant type, Glioblastoma Multiforme (GBM), is usually associated with activating mutations of cell growth signaling pathways and inactivation of cell cycle regulators. However, the contribution to tumor onset and maintenance as well as the relationship that these oncogenic events hold between them is still unclear. Here, we show a gliomagenesis model that contributes to a better understanding of the biology of gliomas. We found that in astrocytes, the hyperactivation of growth signaling pathways, mediated by the constitutively activated isoform of Ras, increases cell proliferation rate, stimulates reactive oxygen species (ROS) formation and generates genomic instability. We also observed that these astrocytes were able to induce tumor formation in vivo, resembling low-grade gliomas. However, this outcome differs when oncogenic Ras is accompanied by the deregulation of cell cycle through the inactivation of the tumor suppressor retinoblastoma (Rb). We provide evidence that Rb is a key partner of Ras oncogenic activity enhancing the response against DNA damage and at the same time blocks cellular stress pathways, which allows the cell to escape from programmed cell death and senescence. This results in in vivo formation of a tumor that recapitulates human GBM features. We propose that Rb may act as a modulator in the transition between low-grade and high-grade gliomas.