Ras和mTOR是细胞中重要的信号激酶，在肿瘤的发生、发展和凋亡中起着重要的作用，而且两者在细胞自噬中也具有关键的调节作用。肾细胞癌对于化疗不敏感，靶向治疗成为晚期肿瘤的主要治疗手段。尽管有研究发现肾癌中mTOR过度激活，在肾癌细胞中有关mTOR和自噬的关系报道很少。申请人小组的初步结果显示肾癌组织中基础自噬降低，mTOR表达增高，Ras抑制剂可以诱导自噬，提示Ras与mTOR信号通路的相互串扰在肾癌自噬的重要性。因此，我们计划通过实验来了解在肾癌细胞中Ras和mTOR信号串扰的状况和通路上各个信号分子之间的关系。尝试通过抑制Ras信号通路来抑制mTOR通路，观察肾癌细胞自噬的发生情况，以及细胞程序性死亡或者凋亡地发生情况，为肾癌治疗寻找新的靶点积累理论依据。

Both Ras and mTOR play important roles in the cell survival. Especially in tumors, their function are crucial for tumor proliferation or apoptosis. On the other hand, Ras and mTOR are key signal on the upstream of autophagy which regulate the induction of autophagy. The literature showed that mTOR was over activated in renal cell carcinoma. But little is known about its relation with the autophagy in renal cell carcinoma. The applicant group have found the autophagy was inhibited in RCC compared with normal renal tissue and Ras antagonist could induce the autophagy via mTOR pathway. Based on the preliminary findings, we would like to carry out the following research with the grant support: (1)To describe the autophagy status in renal cell carcinoma;(2)to figure out the function and signal pathway of autophagy in RCC; (3)to acknowledge the crosstalk between Ras and mTOR in RCC, and their interaction on autophagy and apoptosis of RCC cells.