Ink4a-Arf Loss Cooperates with KRas Activation in Astrocytes and Neural Progenitors to Generate Glioblastomas of Various Morphologies Depending on Activated Akt

摘要: Deletion of the INK4a-ARF locus is found in majority human malignant gliomas. However, role loss gliomagenesis unclear. Animal modeling has shown that mice with targeted deletions Ink4a-Arf gene do not develop spontaneous We have previously reported combined KRas and Akt signaling could induce glioblastoma (GBM) formation from neural progenitor cells but had no effect differentiated astrocytes. In this investigation, we studied effects on GBM induced by transfer into show here deficiency allows for astrocytes it enhances tumor incidence cells. Furthermore, alone can cooperate deletion both The resulting tumors were nestin positive resembled a spectrum glioma morphologies ranging astrocytic character depending cell-of-origin presence activated Akt. Our data strongly supports view one be to sensitize transformation through dedifferentiation response appropriate oncogenic stimuli.