Involvement of Autophagy in Oncogenic K-Ras-induced Malignant Cell Transformation

摘要: Autophagy has recently been implicated in both the prevention and progression of cancer. However, molecular basis for relationship between autophagy induction initial acquisition malignancy is currently unknown. Here, we provide first evidence that essential oncogenic K-Ras (K-RasV12)-induced malignant cell transformation. Retroviral expression K-RasV12 induced autophagic vacuole formation transformation human breast epithelial cells. Interestingly, pharmacological inhibition completely blocked K-RasV12-induced, anchorage-independent growth on soft agar. Both mRNA protein levels ATG5 ATG7 (autophagy-specific genes 5 7, respectively) were increased cells overexpressing K-RasV12. Targeted suppression or by short hairpin (sh) RNA inhibited agar tumor nude mice. Moreover, reactive oxygen species (ROS) with antioxidants clearly attenuated K-RasV12-induced induction, autophagy, MAPK pathway components activated K-RasV12, JNK blunted subsequent autophagy. In addition, pretreatment activation. Our results novel critically involved show species-mediated activation plays a causal role through up-regulation ATG7.