Akt signaling is required for glioblastoma maintenance in vivo

作者：Robinson James P; VanBrocklin Matthew W; McKinney Andrea J; Gach H Michael; Holmen Sheri L^*

来源：American Journal of Cancer Research, 2011, 1(2): 155-167.

• Akt
• Ras
• glioma
• mouse model
• tumor maintenance
• somatic cell gene delivery
• retroviral vector
• RCAS
• TVA

Glioblastoma multiforme (GBM) can be induced in mice through the combined expression of activated forms of KRas and Akt in glial progenitor cells. We have previously demonstrated that KRas is required for the maintenance of these tumors in vivo as inhibition of KRas expression resulted in apoptotic tumor regression and significantly increased survival. To determine the reliance of these tumors on Akt signaling in vivo, we generated a viral vector that allows the expression of Akt to be controlled post-delivery. Survival rates were compared between those animals with continued Akt expression and animals in which expression of Akt was suppressed. Although a fifth of the tumors were refractory to treatment, inhibition of Akt significantly increased the survival of tumor-bearing mice and nearly a fourth of the mice remained in remission four months after the treatment period. These data suggest that Akt is required for glioblastoma maintenance in the context of activated Ras and that loss of Akt expression results in increased survival; therefore, the PI3K/AKT signaling pathway is a viable therapeutic target in this context.

• 出版日期2011