论文部分内容阅读
Autophagy, a process known to provide a survival advantage to the cells undergoing various stresses, has been recently linked to the actual death process.In our study, Ha-ras overexpression in mouse NIH3T3 and mouse embryo fibroblast (MEF) cells induces autophagy.However, the former formed tumors significantly while injected into SCID mice.Moreover, Ha-ras overexpression in MEF autophagy related gene 5 knock-out Atg5(-/-) cells induced tumor formation in mice.Together, it indicates that the threshold of Atg5 expression level may play an important role in Ha-ras-related tumorigenesis.BCL2/adenovirus E 1B 19KDa interacting protein 3 (BNIP3), a pro-apoptotic gene is up-regulate by Ha-ras through the Raf/ERK signaling pathway.Ha-ras induced autophagy is through up-regulation of BNIP3 at the transcription level.In addition, Ha-ras overexpression triggered ER stress only partially participated in autophagy.Ha-ras overexpression induced autophagic flux both in vitro and in vivo.All together, we reveal that Ha-ras utilizes Raf-1/ERK signaling pathway to activate BNIP3 and subsequently to induce an autophagic flux both in cell and in tumor.The relationship among Ha-ras, autophagy and tumor formation will be further clarified.