p53在脂质代谢中的调控作用研究

Initiation and progression of tumor is a complicated and continuous progressive process, during which the cell metabolism pattern is altered andmetabolism rearrangement occurs as an adaption to the rapid proliferation of tumor cells. Endogenous molecules in metabolism pathways play a critical role in the development of tumor. p53 gene is the tumor suppressor hitherto most closely related to human cancer, however, present studies on cell cycle and apoptotic target genes explain only parts of the anti-tumor mechanism of p53. There have been extensive studies reporting the regulation of metabolism by p53. Few of them, however/nonetheless, investigated the impact of p53 on lipid metabolism. We establish the first p53-R277K mutation knock-in mice model and we observed the occurrence of lymphoma and sudden death at4-5 monthsin homozygous mice. This project, using the p53-R277K mutation knock-in andp53 knockout mice models as the entry point, aims at investigating the regulation effect of p53 on lipid metabolism and has pivotal importance inrevealing the initiation and development process of tumor and will therefore provide greatclinical significancein tumor therapeutic strategy.

肿瘤的发生发展是一个复杂的进行性过程，在这个过程中细胞的代谢模式发生改变，产生代谢重排以满足肿瘤细胞快速增殖的需求。各代谢通路中内源性小分子物质在肿瘤的进程中起着非常关键的作用。p53 是迄今发现与人类肿瘤相关性最高的抑癌基因,但是目前对其细胞周期、凋亡靶基因的研究尚无法完全解释 p53 抑制癌症的机理。p53对代谢的调控已有诸多报道，但是p53对脂代谢的调控却鲜有研究。我们首次建立了p53基因突变小鼠模型p53-R277K，发现Homo小鼠有淋巴瘤发生并在4-5月龄大时突然死亡。本项目以基因突变小鼠模型p53-R277K以及p53 KO小鼠模型为切入点，研究p53对脂质代谢的调控作用，对于揭示肿瘤发生发展过程、寻求科学的治疗策略具有非常重要的意义。