p53与Ras协同及其在肿瘤发生中的作用

肿瘤发生是抑癌基因失活和原癌基因激活共同作用的结果。p53基因被认为是目前最重要的抑癌基因, 50%以上的肿瘤中存在p53基因的点突变现象; 而Ras基因是肿瘤中突变率较高的原癌基因, 其突变率在某些肿瘤中高达30%~90%。研究发现, 肿瘤发生过程中抑癌基因p53与原癌基因Ras之间存在复杂的相互协同作用。根据目前的文献报道, p53与Ras之间的协同作用可以分为3种：第一, p53对Ras的调节作用; 第二, Ras对p53的调节作用; 第三, p53和Ras共同调控某些与肿瘤发生相关的关键基因。了解p53与Ras之间的3种调控作用将有助于我们进一步认识p53失活与Ras激活协同促进肿瘤发生的分子通路和机制, 同时也将为癌症的个性化治疗和药物靶点的选择提供重要依据。因此, 文章将对近年来所发现的p53与Ras的各种协同作用机制及其与肿瘤发生的关系进行概括和综述。

The cooperation between p53 and Ras in tumorigenesis

Inactivation of the tumor suppressor gene and activation of the oncogene cooperate to promote the multistep process of tumorigenesis. p53 is considered to be the most important tumor suppressor gene. p53 is usually found as a result of somatic missense mutation in approximately 50% of human cancers. Ras is found to be one of the most frequently mutated oncogenes in human tumors with the reported frequencies ranging from 30% to 90%. It has been found in many studies synergistic effect between tumor suppressor p53 and oncogene Ras occurs during the multistep process of tumorigenesis. According to the current reports, the cooperative effect between p53 and Ras can be divided into three types: the regulation of p53 for Ras function, , the regulation of Ras for p53, and the cooperation between p53 and Ras to control critical genes that are closely related to tumorigenesis. Understanding their synergistic effects will not only help us further disclose mechanism of tumorigenesis caused by p53 inactivation and Ras activation, but also facilitate personalized treatments and pharmacological target selection for cancer therapy. Therefore, we reviewed the recent progress of synergistic effect between p53 and Ras and its role in tumorigenesis.