甲状腺激素受体(TR)基因突变及其下游通路与肿瘤相关研究进展

Progress on the thyroid hormone receptor gene mutation and its downstream pathways associated with tumor

信号通路是研究肿瘤发生发展、预防及治疗的重要领域之一,现已证实MAPK和PI3K等通路是肿瘤发生发展的重要信号通路,甲状腺激素(TH)及其受体(TR)可以影响这些通路起到抑制癌细胞生长和转移的作用,并逐渐成为研究的热点。而研究发现多种肿瘤存在TR基因突变现象,TR基因突变影响了TH/TR调解下游通路的功能,并成为下游原癌基因激活的诱因。近年研究发现了TH/TR介导的β-连环蛋白(β-catenin)降解机制,不仅丰富了它们在肿瘤发生发展中的作用,并进一步为突变受体对下游原癌基因的持续激活提供了理论依据。相信随着对其下游通路研究的进一步深入,最终会指导临床,为肿瘤预防和分子靶基因治疗提供新的理论依据。

Signaling pathways such as MAPK and P13K have been confirmed to be important in the mechanism of tumor genesis,development,prevention and treatment.Thyroid hormone（TH）and its receptor（TR）can affect the pathways resulting in inhibition of tumor growth and metastasis,thus they have gradually become the focus of recent research.However,numerous studies showed that TR gene mutation was often observed in a variety of cancers and resulted in the deregulation of TH/TR mediated downstream pathways,and TR gene mutation became an causative agent to activate downstream proto-oncogene.Recent studies showed that TH/TR might play a role in the regulation of β-catenin degradation,the knowledge of which allows us not only to further understand the function of TR gene in the inhibition of tumor development,but also provide a theoretical basis for the continuous activation of downstream proto-oncogene by TR mutation.To study the downstream pathway of TR gene could eventually guide the clinician and provide a new theoretical basis for cancer prevention and molecular target gene therapy.