Ha-ras Oncogene Induces Autophagy and Its Role in Tumorigenesis

• 作 者: Hsiao-ShengLiu;
• 机 构: Departments of Microbiology and Immunology Institute of Basic Medical Sciences College of Medicine N
• 出 处: BIT‘s2nd Annual World Cancer Congess-2009 (2009第二届癌症大会)
• 发表日期: 2009年期

　　We have demonstrated that overexpression of Ha-rasval 12 oncogene induces autophagy in NIH3T3 cells.BNIP3 (Bcl-2/adenovirus E1B 19-kDa interacting protein 3) is a hypoxia-induced pro-death protein that belongs to the Bcl-2 superfamily.We reveal that Ha-rasval 12 up-regulates BNIP3 at transcription level and is through Ras/Raf-1/Erk signaling pathway.Furthermore, Ras-induced autophagy is through Ras/Raf-1/Erk/BNIP3 signaling pathway.In addition, ER stress was also induced by Ha-rasval 12 overexpression and is partially involved in Ras-induced autophagy.Our in vivo study shows that NIH3T3 cells overexpressing Ha-rasval 12 induce tumor formation in SCID mice.These mice were sacrificed at day 17 and the protein extracted from the tumors was analyzed, and LC-3 type Ⅱ protein expression (an indicator of autophagosome formation) was detected.All together, our data demonstrate that Ha-rasval 12 overexpression induces autophagy both in vitro and in vivo through Ras/Raf-1/BNIP3-and ER stress-related signaling pathways.The role of autophagy in Ras-related tumorigenesis is under investigation.